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PULMONARY HYPERTENSION
Introduction
Pulmonary hypertension (PH) is characterised by an elevation of the arterial pressure and vascular
resistance within the pulmonary circulation. Pulmonary hypertension is recognised as a complex and
multidisciplinary disorder in people and this is even more so in small animals due to the paucity of
appropriate studies.
In veterinary medicine, PH has been described as echocardiographically-estimated pulmonary
arterial systolic pressure (based on a peak systolic tricuspid regurgitation gradient) greater than 30
mmHg. In people, specific hemodynamic criteria include systolic pulmonary arterial pressure (PAP)
>30 mmHg, diastolic PAP >20 mmHg, mean PAP >25 mmHg, pulmonary capillary wedge pressure <15
mmHg.
Pre and Post capillary PH
Pre-capillary PH should be distinguished from Post-capillary PH.
Pre-capillary PH is characterised by an isolated elevation of PAP with normal pulmonary capillary
pressure (PCP). Since in this setting, the pulmonary hypertensive state is limited to the arterial
component of the pulmonary vasculature, pulmonary arterial hypertension (PAH) is distinguished
from other forms of PH.
In contrast, post-capillary PH is caused by diseases affecting the left side of the heart with secondary
pulmonary venous congestion, which in turn leads to an elevation of PCP and PAP.
The most important consequence of PH is chronic overload of the right heart (cor pulmonale) which
ultimately leads to right heart failure and is thus responsible for the poor prognosis of patients with
severe PH. Because of the complex pathophysiology, the importance of a proper diagnostic
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evaluation and to establish a precise diagnostic classification, and the dynamic development of
therapeutic recommendations, patients with pulmonary hypertension should be assessed by
experienced clinicians.
Aetiology and Pathophysiology
The ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension, defines PH as a
syndrome resulting from restricted flow through the pulmonary arterial circulation and resulting in
increased pulmonary vascular resistance (PVR) and ultimately in right-sided heart failure. The
predominant cause of increased PVR is loss of vascular luminal cross section due to vascular
remodelling produced by excessive cell proliferation, although excessive vasoconstriction plays a
significant role in approximately 20% of human patients. Improved understanding of the disease
pathways in PAH, even if a single primary cause remains elusive, has led to therapeutic strategies,
including the administration of prostanoids, the antagonism of endothelin receptors, and inhibition
of PDE-5 (which is currently the most used therapeutic intervention in veterinary medicine).
Histologically, PAH is characterised by a variety of arterial abnormalities, including intimal
hyperplasia, medial hypertrophy, adventitial proliferation, thrombosis in situ, varying degrees of
inflammation. An individual patient may manifest all of these lesions, and the distribution of lesions
may be diffuse or focal.
The right ventricular (RV) function is a major determinant of functional capacity and prognosis in
PAH. While RV hypertrophy and dilatation are initiated by increased afterload (i.e., elevated
PVR), the adequacy of the RV’s compensatory response (preservation of stroke volume) is quite
variable amongst individuals and it is unclear why some patients compensate while others
decompensate with clinical manifestations of right-sided heart failure.
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Table: Classification of pulmonary hypertension (adapted from Glaus T, BSAVA 2012)
Group 1
Group 2
Group 3
Group 4
Pulmonary arterial
Pulmonary
Pulmonary
Pulmonary
hypertension (PAH)
hypertension
hypertension
hypertension due
associated with
associated with
to
left heart
respiratory disease
thromboembolic
disease
and/or hypoxemia
disease
Idiopathic (formerly
Left ventricular
Interstitial lung
Primary cardio-
primary PH, PPH)
or atrial disease
disease, e.g.
vascular lesion,
pulmonary fibrosis
e.g. D. immitis, A.
Group 5
Miscellaneous
vasorum
Associated with
Left-sided
Chronic upper
Medical condition
congenital systemic-
valvular disease
airway obstruction
predisposing to
to-pulmonic shunts
pulmonary
thromboembolism
Persistent pulmonary
Chronic exposure to
hypertension of the
high altitude
newborn
Associated with
drugs, toxins,
inflammation
Clinical Signs
Clinical presentation of dogs and cats with PVH are often nonspecific and are mainly characterised
by exercise intolerance, respiratory distress, abdominal distension, occasional cough and syncopal
episodes. However, it is almost impossible to establish whether the clinical signs are caused by the
underlying disorder or the PH per se.
If right-sided heart failure develops, signs may include jugular pulsation, abdominal enlargement
(hepatomegaly and ascites), pleural effusion, arrhythmias.
Diagnosis
Thoracic radiography
It can occasionally identify signs referable to PH as well as signs of potential underlying causes. The
dorsoventral view is probably more helpful to identify right ventricular (“inverted D” shape of the
heart) and enlargement of the main pulmonary artery. Peripheral pulmonary vasculature may be
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tortuous and engorged. Left atrium is enlarged and pulmonary veins are congested with underlying
left atrial, ventricular or mitral valve disease. Signs of underlying bronchial, interstitial or alveolar
pulmonary disease may also be observed.
Echocardiography
It is necessary to confirm or rule out many causes of PH, including acquired left ventricular heart
disease (mitral endocardiosis, dilated cardiomyopathy) and congenital cardiovascular shunts. It
allows confirmation of PH qualitatively and quantitatively:
Qualitative assessment: dilation of right ventricle and right atrium, thickening of right ventricular
wall and papillary muscles, paradoxical septal motion, and decreased left ventricular chamber size.
Quantitatively: in the absence of pulmonic stenosis, the Doppelr identification and quantification of
tricuspid regurgitation will correlate to right ventricular systolic pressure (= systolic PAP) by using the
modified Bernoulli equation (PAP = 4 x V2max, assuming that right atrial pressure approximates zero
mmHg in systole). Therefore if TR Vmax is 2.8 m/s the PAP should be >30 mmHg indicating PH.
Diastolic PAP is calculated with Doppler quantification of pulmonary valve insufficiency (PI); PH is
considered to be present when end-diastolic PI-PG is >20 mmHg (Vmax >2.2 m/s).
Finally, PH can be suspected on spectral Doppler interrogation of the pulmonic flow. A normal
pulmonary artery velocity flow profile should have a dome-like profile with the peak velocity flow
occurring in mid-systole with symmetric acceleration and deceleration phases. If the peak velocity
flow is asymmetric occurring early in systole with a steep and rapid acceleration phase and slower
deceleration or with a notch occurring in the deceleration phase, PH should be suspected.
Values of AT: ET  0.31 for and an AT value of  58 ms are also predictive of PH (AT= acceleration
time, ET= ejection time).
Advanced or confirmatory testing
Contrast ultrasound (bubble study) of the heart and descending aorta to rule out a cardiovascular
right-to-left shunt. Shunting is also possible in congenital pulmonary arteriovenous fistulas or in
acquired pulmonary arteriovenous shunting, such in A. vasorum infection. In this case, bubbles will
take at least 3 cardiac cycles from their appearance in the right atrium till their appearance in the
left atrium.
Right-sided cardiac catheterisation for invasive measurement of pulmonary wedge pressure as an
estimate of left atrial pressure, and systolic and diastolic pulmonary artery pressure.
Pulmonary CT to identify/rule-out parenchymal disease and Angio-CT for PTE.
Pulmonary ventilation-perfusion scintigraphy to rule out PTE
Pulmonary histopathologic evaluation to confirm PAH
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Current therapeutic options for PH
The therapeutic target remains the identification and removal of the primary cause of PH (e.g.
removal of heartworms, thrombolysis in pulmonary thromboembolism, etc). Secondary target is to
improve oxygenation (Oxygen, cage, nasal or mask) and reduce the vascular resistance
(vasodilation).
As far as I am aware, there are no controlled studies to prove the efficacy of any medical treatment
in naturally occurring PH in dogs or cats, however, all the following treatments have been indicated
as potentially beneficial for lowering PAP:

Amlodipine (Istin, Norvasc) in moderate PH, starting at 0.05 mg/kg PO SID

Sildenafil (Viagra) in severe PH, 2–3 mg/kg PO BID or TID.

Pimobendan (Vetmedin, Cardisure), 0.1-0.3 mg/kg BID.
Further reading
ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American
College of Cardiology Foundation Task Force on Expert Consensus Documents and the American
Heart Association: developed in collaboration with the American College of Chest Physicians,
American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation (2009)
119:2250-94.
Glaus T. Pulmonary hypertension - pathophysiology, diagnosis and treatment. Proceedings BSAVA
Annual Congress, Birmingham 12-15 April 2012
Kellum HB and Stepien RL. Sildenafil citrate therapy in 22 dogs with pulmonary hypertension. J Vet
Intern Med. 2007 Nov-Dec;21(6):1258-64
Rosenkranz S. Pulmonary hypertension: current diagnosis and treatment. Clin Res Cardiol (2007)
96:527–541
Schober KE and Baade H. Doppler echocardiographic prediction of pulmonary hypertension in West
Highland white terriers with chronic pulmonary disease. J Vet Intern Med 2006;20:912–920
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SYSTEMIC HYPERTENSION
Introduction
Systemic hypertension is a sustained increases in blood pressure (BP). In veterinary clinical settings
this can be caused by artefacts (ie, stress-induced or white-coat hypertension) or be secondary
clinical conditions that are accompanied by increased BP (secondary hypertension). Primary or
idiopathic hypertension is also possible but this represents a rare condition in small animal medicine.
White Coat Effect
The artefactual increase in BP (“white-coat effect”) occurs as a consequence of the measurement
process, generally due excitement or anxiety which evoke the sympathetic response of the
autonomic nervous system. Since this condition represents a natural physiological response, the
hypertension tends to resolve once the cause/artefact has been eliminated (eg, altering
measurement conditions to reduce the animal’s anxiety or measuring BP at the animal’s home).
Anxiety-induced increases in BP can lead to a false diagnosis of systemic hypertension.
Unfortunately, the effects of anxiety on BP are not predictable, as some animals exhibit a dramatic
increase in BP whereas others do not, and some animals may even exhibit a decrease in BP as a
result of the measurement process. The latter effect presumably is due to parasympathetic nervous
system over-activity.
Secondary Hypertension
This type of hypertension represents a secondary effect of another underlying clinical condition (eg
renal disease, hyperadrenocorticism, diabetes, obesity, pheochromocytoma, hyperthyroidism), or
could represent a side-effect of an hypertensive medication (eg glucocorticoids, mineralocorticoids,
erythropoietin, sodium chloride, phenylpropanolamine, and nonsteroidal anti-inflammatory drugs).
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The presence of a condition known to cause secondary hypertension, even if effectively resolved by
therapeutic intervention, should prompt serial follow-up evaluations.
Primary (idiopathic) hypertension
The term describes the presence of hypertension in the absence of any identifiable predisposing
causes. It is rare in small animals, although it has been reported in dogs. However, it may also be
caused by subclinical kidney disease, making diagnosis of primary hypertension exteremely
challenging. Therefore, the term “idiopathic” is probably more accurate than primary in the
veterinary clinical settings. A diagnosis of idiopathic hypertension is established when reliable BP
measurements demonstrate a sustained increase in BP concurrent with normal CBC, serum
biochemistry, and urinalysis, although hypertension may also induce polyuria (“pressure diuresis”).
Other diagnostic tests may be indicated, such as renal and adrenal ultrasound examination,
measurement of glomerular filtration rate, quantitative assessment of proteinuria, T4
determination, and adrenal function tests. Although secondary hypertension remains the most
common category of high BP in dogs and cats, idiopathic hypertension is more common than
previously recognised, accounting for approximately 18–20% of cases in cats.
Isolated Systolic or Diastolic Hypertension
These terms refer to the occurrence of an increase in systolic only or diastolic only pressure. Such a
finding may be artefacts produced by under/over-estimation of the peak or trough of the blood
pressure curve by an indirect device. The presence of this type of artefact should be considered
whenever a very small (,20 mm Hg) or large (.60 mm Hg) pulse pressure is reported by an indirect
device. Currently, in veterinary medicine, there is an emphasis on the diagnosis of systolic
hypertension, primarily because the most common technique (Doppler) only provides systolic
readings. Systolic BP is an important determinant of hypertensive tissue damage in small animals.
However, isolated systolic and diastolic hypertension can and do occur in dogs and cats and, when
properly diagnosed, warrant classification and management.
Target Organ Damage (TOD)
Sustained increases in BP cause injury to tissues and the rationale for treatment of hypertension is
the prevention of such injury (end-organ or target-organ damage). In the kidney, for example, TOD is
generally manifested as an enhanced rate of decrease in renal function, early renal death, and
proteinuria or some combination of these findings. The severity of albuminuria has been directly
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related to the degree of increase in BP in an experimental study of chronic kidney disease (CKD) in
cats.
Proteinuria has also been directly related to the extent of increase in BP and to the rate of decrease
in GFR in an experimental study in dogs. The magnitude of proteinuria is a negative prognostic factor
in spontaneous feline CKD and reduction of proteinuria is perhaps the most reliable evidence of
benefit in an animal treated with antihypertensive agents, particularly in cats.
Ocular lesions, often accompanied by acute blindness, are observed in many cats with hypertension,
and although prevalence rates for ocular injury vary, it has been reported to be as high as 100%!
Encephalopathy has been reported in small animals as a consequence of cerebral oedema and
haemorrhage. Observed clinical signs are typical of intracranial disease and include lethargy,
seizures, acute onset of altered mentation, altered behaviour, disorientation, balance disturbances
(eg, vestibular signs, head tilt and nystagmus), and focal neurologic defects due to stroke-associated
ischemia.
Cardiac changes in hypertensive animals are frequent and may include systolic murmur, gallop
rhythm, and left ventricular concentric hypertrophy (LVH). Effective antihypertensive therapy may
decrease the prevalence of LVH in affected dogs and cats.
Epistaxis, presumably due to hypertension-induced vascular abnormalities, has been associated with
systemic hypertension in people but it is rarely observed in small animals.
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Blood pressure measurement
Measurement of arterial blood pressure allows an objective and definitive diagnosis of hypertension.
Blood pressure measurements can be obtained either by direct or indirect measurements. Direct
(invasive) technique requires the catheterisation of an artery and is mostly used for anaesthetic
monitoring. Indirect (non invasive) procedures are more appropriate for use in the majority of
clinical cases since they do not require sedation or anaesthesia and involve minimal stress to the
patient. Two successful non-invasive methods are represented by Doppler and oscillometric
techniques. On the contrary, the auscultatory technique commonly used in people, is unsuitable in
small animal medicine, as the frequency of the sound associated with blood flow to a limb is too low
to be audible just with a stethoscope.
Blood pressure readings can be taken from the forelimb, the hindlimb and the tail. The author
prefers to use the common digital artery on the forelimb. For blood pressure recording in this
location, a cuff with a width approximately 40% of the circumference of the limb is placed around
the forelimb between the elbow and the carpus.
Doppler technique
A small quantity of ultrasound gel is applied to the palmar surface of the forelimb between the
carpal and metacarpal pads area to allow better detection of the Doppler signal. In some cases, the
area in proximity of the artery needs to be clipped. The Doppler probe is gently placed onto the
prepared area and moved until the pulse can be heard. Once a good signal has been obtained, the
cuff is inflated using the hand-pump sphygmomanometer to a pressure of around 30 mmHg above
the point at which the pulse can no longer be heard. The cuff is then slowly deflated and the
pressure gauge observed. The reading at which the pulse is first heard to return is taken to be the
systolic blood pressure (SBP). This procedure is repeated 5 times over 2-3 minutes and the SBP taken
as an average of these readings.
Oscillometric technique
The oscillometric system is characterised by an automatically inflated and deflated cuff. During
deflation, variations in cuff pressure are sensed by a transducer. This system is very easy to operate
and also offers the advantage of giving diastolic as well as systolic blood pressure readings. On the
other hand, errors can result if the patient moves or if significant arrhythmias are present.
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Management of the hypertensive patient
Underlying diseases that may be causing secondary hypertension should be identified and treated
while continuing to monitor BP. With the exception of advanced cerebral hypertensive damage,
antihypertensive therapy generally is not an emergency intervention.
A decision to treat is made on the basis of categorization of TOD risk.
As hypertension in dogs and cats is most often secondary, antihypertensive drug therapy by itself is
often not sufficient and initial considerations should always include the identification and
management of conditions likely to be causing secondary hypertension and the identification and
treatment of TOD.
Although frequently recommended as an initial step in the pharmacological management of high BP,
dietary salt restriction is controversial and the available evidence suggests that substantial sodium
restriction alone generally does not reduce BP. In fact, sodium restriction may activate the reninangiotensin-aldosterone axis (RAAS) and eventually increase BP
ACEinhibitors (ACEI) and calcium channel blockers (CCB) are the most widely used antihypertensive
agents in veterinary medicine.
In dogs, ACEI are usually recommended as the initial agent of choice. Since ACEI preferentially dilate
the efferent arteriole, they lower the intraglomerular pressure and frequently decrease the
magnitude of proteinuria. However, ACEI should not be used in dehydrated patients in which the
GFR might drop precipitously. These patients should be carefully rehydrated and then re-evaluated
before instituting antihypertensive therapy.
If primary causes of systemic hypertension have been ruled out, administration of amlodipine can be
considered. Initial dose is 0.05-0.1 mg/Kg SID or BID. The dose can be titrated upwards weekly as
required up to 0.4 mg/Kg, monitoring blood pressure regularly.
In cats, although the RAAS axis may play a role in the genesis or maintenance of systemic
hypertension, CCB are often the first choice for antihypertensive therapy due to established efficacy
(e.g. amlodipine 0.625-1.25 mg/CAT SID. The dose may be increased slowly or the frequency
increased to BID if necessary). Blood pressure monitoring is essential. A mean decline in systolic BP
of 40–55 mm Hg is typically observed in cats with moderate-to-high risk of TOD. Despite significant
antihypertensive efficacy, CCB have not been shown to increase survival time in treated cats and
their use may activate the systemic or intrarenal RAAS. A key predictive factor is the effect on
proteinuria.
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The co-administration of ACEI and CCB is another possibility.
Although diuretics are frequently administered to hypertensive people, these agents are not firstchoice drugs for veterinary patients with CKD, in which dehydration and volume depletion may
prove problematic.
References
Brown et al. Guidelines for the Identification, Evaluation, and Management of Systemic
Hypertension in Dogs and Cats. J Vet Intern Med 2007;21:542–558
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FELINE AORTIC THROMBOEMBOLISM
Introduction
Arterial thromboembolism (ATE) is characterised by the embolisation of a clot in an artery in the
systemic circulation. The artery in which the clot will eventually lodge depends on the origin of the
clot itself, its size and the diameter of the artery. In most cases, the initial blood clot forms inside the
cavities of the left heart, particularly in the left auricle. The clot, or a fragment of it, can
subsequently flow to an anatomical location in the systemic arterial circulation, normally
represented by a ‘‘saddle’’ location at the aortic trifurcation, and subsequently compromising the
blood flow in both external iliac arteries. Occasionally, emboli may travel into more distal arteries,
compromising the blood flow to a single limb, including forelimbs. More rarely, ATE affects cerebral,
renal, and mesenteric arteries. The majority of cats presenting with ATE have underlying heart
disease, although neoplasia (hepatocellular carcinoma, pulmonary carcinoma, anaplastic carcinoma,
vaccine-associated fibrosarcoma, and squamous cell carcinoma) and thyroid disease are also highly
associated with ATE.
Clinical presentation
The classic clinical presentation is characterised by acute pain and paresis/paralysis of the affected
limbs. The paws of the affected limb may appear pale or cyanotic depending on the severity of the
local ischemia, and the limb extremity is generally colder than non-affected limbs. In most cases the
“saddle” thrombus obstructs the external iliac arteries and consequently femoral pulses are weak or
absent. However, if the thrombus lodges across the internal iliac arteries femoral pulses may still be
palpable despite the presence of painl and hind limb paralysis/paresis.
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Conversely, the femoral pulsation may be difficult to be detected in cats with shock, therefore the
use of a Doppler transducer may assist the clinician in the identification of the arterial pulsation in
the affected limb.
Diagnosis
Diagnosis of ATE can be challenging and it is usually based on history and clinical signs. In cats
spending most of their time outdoors, the patient can be found recumbent on the ground and the
owner’s initial thought is often towards a road traffic accident. Indeed, neurological disorders and
musculo-skeletal injuries are important differential diagnoses.
In these patients, marked elevations of AST and CK are highly suggestive of ischemic damage to the
limb skeletal muscles. In cats, both AST and CK have short half-lives, and their values peak at 6-12
hours, returning to normal within 24-48 hours after the acute ischemic event.
Thoracic radiographs may reveal cardiomegaly and signs of CHF (pulmonary oedema and/or pleural
effusion). Echocardiography allows identification of concomitant heart disease and, sometimes,
confirms the presence of a thrombus or spontaneous echo-contrast (smoke) within the heart
chambers. The localisation of the thrombus can be deduced from the affected limb and, in many
cases with hindlimb paralysis/paresis, where available, colour Doppler ultrasound examination of
the descending aorta can be used to visualise the point of obstruction.
Clinical management
There is little scientific evidence and no consensus amongst clinicians regarding the ideal treatment
of cats affected by ATE.
Surgical embolectomy would appear the most logical approach, but is difficult due to the size of the
affected vessels and the anaesthetic risks encountered in cardiac patients. It is also an extremely
unrewarding technique due to the high mortality associated with rapid reperfusion (reperfusion
injury). This complex phenomenon occurs when a large ischemic area is acutely reperfused,
accompanied by a violent inflammatory response within damaged tissues and leakage of cellular
metabolic waste products into the circulation. Physical thrombolytic therapy may also appear as a
rational intervention. This can be performed with pressurised saline jets to physically dissolve the
thrombus (AngioJet Rheolytic Thrombectomy) with clinical outcome comparable with conventional
therapies. Medical thrombolytic therapy (urokinase, streptokinase and tissue plasma activator -TPA)
has shown mixed results, especially because of complications due to rapid reperfusion. In analogy
with myocardial infarction in people, these expensive drugs are only effective if administered within
hours of the occurrence of ischemia, which is rarely possible in veterinary patients.
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Conservative treatment is commonly recognised as an acceptable management for feline ATE cases,
as long as pain is optimally controlled and patients undergoing treatment are properly selected. The
rationale of conservative treatment is to support the patient until the development of collateral
circulation to provide sufficient blood supply to the ischemic areas. The time necessary for a
satisfactory clinical improvement depends on the severity of the insult and the underlying cause and
may range from days to months. Euthanasia should be considered in cases of non-responsive
patients (lack of clinical improvement after 2-3 days or unsatisfactory pain control) or for those
exhibiting signs highly associated with a negative prognosis (severe hypothermia, multiple limbs
affected with complete loss of motor function, concurrent CHF). The fact that feline ATE is a
devastating clinical manifestation is undisputable. However, if euthanasia with no attempt to treat is
excluded from survival analyses, the number of cats that can survive to discharge can increase up to
40-70%.
Parameters that should be evaluated to select potential survivors are:
•
rectal temperature above 37.2 °C (98.9 °F)
•
presence of limb motor function as evidenced by voluntary movement of limbs or positive
withdrawal reflex
•
absence of radiographic signs of congestive heart failure (CHF) such as pulmonary oedema,
pleural effusion
•
single limb affected (rather than two or more)
•
absence of tachycardia (i.e. HR < 180 bpm)
•
absence of hyperkalaemia (i.e. potassium < 5 mmol/l)
Of all the above parameters, rectal temperature is the strongest survival predictor, indicating that
hypothermia is most likely a reflection of compromised systemic hemodynamic status rather than
just local hypo-perfusion.
Short-term, in-hospital, conservative management
The goal of conservative treatment of ATE is to:
•
guarantee adequate rest and pain relief
•
reduce the risk of further thrombus formation
•
improve systemic perfusion and preserve the function of the affected limbs
•
control effusions in cases complicated by CHF
•
provide additional support where needed
The ideal analgesic for cats affected by ATE probably depends on different patient responses,
individual clinician’s experience and drug availability. However, a variety of successful analgesic
drugs have been reported, including butorphanol, buprenorphine, morphine, and fentanyl. A
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common protocol adopted in veterinary practice is intravenous or sublingual buprenorphine
administration followed by application of a fentanyl patch to allow consistent and prolonged
analgesia.
Intravenous or subcutaneous unfractionated heparin (UFH) can be considered during the acute
phase (hospitalisation period) due to the rapid onset of its anticoagulation properties. Conversely,
intramuscularly administration of heparin should be avoided due to the risk of injection-site
haematomas. Low-molecular weight heparin (LMWH) does not offer any practical advantage over
UFH for short-term treatment. Cats absorb and eliminate LMWH very rapidly and therefore require
higher doses and more frequent injections of the LMWH to achieve the therapeutic effects observed
in human patients. It is also considerably more expensive than UFH.
Correcting systemic perfusion is a challenging task, especially in cats with signs of CHF who should
never receive aggressive fluid therapy. However, if patients are not in CHF and appear dehydrated,
cautious fluid therapy would certainly be indicated. Acepromazine (ACP) has been advocated for
many years as a suitable drug to improve systemic perfusion in cats with ATE. However, it’s
hypotensive effect can also exacerbate the signs of shock and many clinicians consider the use of
ACP inappropriate for cats with ATE. Similarly, external physical warming should only be performed
very cautiously to avoid the risk of peripheral vasodilation and reduction of core perfusion. Little is
known about the benefits of physiotherapy. Deep tissue massage of the affected areas and gentle
forced movements of the affected limbs may be beneficial as long as the manoeuvre does not evoke
pain or discomfort. Soft beds and gentle turning of the patient may also reduce pain and discomfort.
Management of congestive heart failure is described in the previous chapter.
Cats affected by ATE are usually inappetant and nutritional support can be easily achieved via nasooesophageal tubing in cats without respiratory distress.
Long-term, at home, conservative management
When the patient appears sufficiently comfortable and is regaining appetite, discharge can be
discussed. The owner should be prepared to support the cat at home, including hand-feeding,
grooming and toilet assistance.
Cats with an underlying cardiac disease and CHF should receive appropriate chronic treatment.
Similarly, appropriate treatment should be considered in cats affected by hyperthyroidism or
neoplasia.
Prophylactic anti-coagulation therapy has been debated for several years. However, at present,
there is no sufficient scientific evidence to support a specific medication or protocol. Unfractionated
heparin treatment requires frequent parenteral administrations to achieve consistent
anticoagulation and is not generally suitable for home treatment. Oral aspirin is frequently
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prescribed at 75mg (“baby aspirin”) every 72h. However, a lower dose (5mg/cat/q72h) seems
associated with fewer side effects and similar recurrence rate of ATE when compared to the
traditional dose, although a compounding pharmacy is necessary to obtain accurate low dosing. .
Nevertheless, very little is known about pharmacokinetics and clinical efficacy of aspirin in
preventing ATE. Clopidogrel (Plavix®, 18.75 mg/cat PO q 24h) is another inhibitor of platelet
aggregation that seems to have few adverse effects in cats. It is commonly used in veterinary
practice as a daily medication to prevent recurrence of ATE often in association with aspirin.
However, at present, the clinical efficacy of clopidogrel for ATE prevention has not yet been
reported.
Prognosis
Long-term survival is negatively affected by the concomitant presence of CHF or neoplasia. Many
survivors can experience a full recovery. However, a degree of neurologic or muscular dysfunction of
affected limbs may persist in some patients. Recurrence rate of ATE is relatively low (approximately
30%), although these episodes are often fatal or require prompt euthanasia. Congestive heart failure
represents the most common cause of death (or euthanasia) in cats surviving acute episodes of
thromboembolism (median survival time of 77 days, compared to 223 days in cats with ATE without
concurrent CHF).
Further reading
1.
Ferasin L. Cardiomyopathy and congestive heart failure. BSAVA Manual of Feline Practice: A
Foundation Manual. 1st Edition 2013. Wiley Ed.
2.
Smith SA, Tobias AH. Feline arterial thromboembolism: an update. Vet Clin North Am Small
Anim Pract 2004;34:1245-1271
3.
Borgeat K et al. Arterial thromboembolism in 250 cats in general practice: 2004-2012. J Vet
Intern Med. 2014 28:102-8
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CARDIOVASCULAR PARASITES
Introduction
There are essentially caused by two parasites: Angiostrongylus vasorum or Dirofilaria immitis.
Angiostrongylus vasorum
metastrongyloid which causes a serious heart and lung condition in dogs. It is endemic in the dog
population of Ireland, South-West of England and it is also present in Italy and France.
Cycle

the adult worms (2.5 cm) live in the pulmonary artery and right ventricle of dogs.

viviparous: larvae are coughed up, swallowed, and passed in the faeces.

the intermediate host of Angiostrongylus is one (or more) species of slug in which the larval
worms live, and dogs may become infected either by eating the slugs themselves (and some
dogs are known to do this) or by inadvertently ingesting slug faeces.

once in the mammal host, the worms migrate to the right ventricle and pulmonary artery
where they may cause pulmonary artery obstruction, endoarteritis, thrombosis, as well as
parenchymal damage due to larval migration.
Clinical signs

congestive heart failure

lower respiratory signs (cough, haemoptysis, dyspnoea)

regional haemorrhage (including ocular, brain, dental, etc)

DIC may occur in severely affected cases or after sudden death of parasites (parasitic
embolism) after treatment
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Diagnosis

history and clinical signs

radiographs: mixed parenchymal changes (patchy alveolar density and/or diffuse interstitial
pattern). Pulmonary congestion and right heart enlargement may be noted.

echocardiography: severe cases may present with pulmonary hypertension, right ventricular
dilation and hypertrophy.

faecal parasitology (Baermann test)

Larvae in BAL

Angio Detect™ Test (pet-side antigen blood test that’s specific for the detection of
Angiostrongylus vasorum infection)
Treatment

fenbendazole (20 mg/kg daily for 21 days)

imidacloprid/moxidectin (Advocate spot on)

restricted exercise is recommended to reduce the risk of thromboembolism after treatment

oxygen, blood transfusion, dexamethasone (in case of thromboembolism or DIC)
Dirofilaria immitis
It is a large, whitish worm. The females are approximately 30cm long, while the males are 23cm long
with a spirally coiled tail.
Cycle

adults are primarily found in the right ventricle and pulmonary arteries of dogs (rarely cats).

viviparous: the females produce small, vermiform embryos called microfilariae.

they can cross the capillary beds and so are found throughout the vascular circulation

circulating microfilariae are ingested by a female mosquito while taking a bloodmeal from
an infected host (A). These prelarval stage develops in the mosquito into the 3rd stage (L3)
larva (B).

infective L3's migrate from the tubules to the lumen of the labial sheath in the vector's
mouthparts.

development in the mosquito is temperature dependent, requiring approximately two
weeks of temperature at or above 27C (80F).Below a threshold temperature of 14C
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(57F),development cannot occur, and the cycle will be halted. As a result, transmission is
limited to warm months, and duration of the transmission season varies geographically.

during a later bloodmeal on an appropriate host (C), the L3 will exit the labium, enter the
bite wound, and penetrate local connective tissues.

moulting to the L4 ensues within seven days of infection (D).

L4 stages undertake extensive migration through the subcutis, which continues for some 6090 days until the final moult to the immature adult (E).

the juvenile worms migrate to the right heart within a few days of their final moult (F),
presumably carried by the venous circulation.

final maturation and mating occur in the pulmonary arteries, and the adult worms live in the
right heart and pulmonary arteries, where they may survive for up to seven years.

production of microfilariae by inseminated female worms begins approximately six and a
half months (192days) after infection.
Epidemiology
the disease is endemic in many areas of USA, Asia, Australia, Africa and South of Europe. It is not
endemically present in the UK.
Pathophysiology

narrowing and occlusion of the pulmonary arteries due to proliferation of intima (not direct
blockage by the adult worms).

distribution and severity of the lesions depends on both the number and location of adult
worms (caudal lobar arteries are the most heavily infected)

sometimes, worms may be found in the right atrium and ventricles, and the vena cavae

pulmonary hypertension is the major consequence of intimal proliferation
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right ventricular dilation and hypertrophy, as well as ischemia and right ventricular failure,
may also be observed

disruption of the intima of the pulmonary arteries may cause attraction of platelets, and
release of Platelet Derived Growth Factor (PDGF).

PDGF triggers proliferation of medial smooth muscle cells and fibroblasts.
Many filarial nematodes, including Dirofilaria immitis, harbour obligate, intracellular, gram-negative,
endo-symbiotic bacteria belonging to the genus Wolbachia (Rickettsiales). Doxycycline reduces
Wolbachia numbers in all stages of heartworms. Doxycycline administration during the first or
second month following experimental heartworm infection was lethal to third- and fourth-stage
heartworm larvae. In addition, in dogs with adult infections, doxycycline gradually suppressed
microfilaremia. Microfilariae ingested by mosquitoes on dogs treated with doxycycline developed
into third-stage larvae that appeared to be normal in appearance and motility, but these larvae were
not able to develop into adult worms, thus reducing the risk of selecting for resistant
subpopulations.
Clinical signs

can vary from no signs at all to signs of heart failure

heart failure can be acute or gradual, and can lead to ascites, hydrothorax, and
hydroperitoneum.

exercise intolerance (increasing in severity with increasing resistance to pulmonary blood
flow)

chronic coughing, dyspnoea, hemoptysis, and syncope.

pulmonary thromboembolism can occur, and is often a response to dying adult worms,
whether the death of the worms be spontaneous or due to treatment with adulticidal drugs.

thrombi form around a degenerating parasite, and a periarterial granuloma can develop in
the lung parenchyma.
Diagnosis

tachypnoea and coughing with a history of exposure to mosquitoes in an enzootic area

advanced stages: animals can show syncope, haemoptysis, and chronic weight loss with
good appetite. A decreased exercise tolerance will also develop, and is more common than
either the syncope or hemoptysis.

ascites and hepatomegaly will be present in case of heart failure.
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Haematology: eosinophilia and basophilia in the early stage of infection.
Radiography:
enlarged right ventricle
enlarged main pulmonary artery
enlarged peripheral pulmonary arteries
decreased peripheral pulmonary artery taper (i.e. truncation)
tortuous peripheral pulmonary arteries
interstitial/alveolar pulmonary pattern with a caudal lobar distribution
Echocardiography:
worms may be seen in the right heart and main pulmonary artery
dilatation and thickening of the right ventricle

Traditionally, the first line of diagnosis for heartworm infection has been a parasitological
examination, looking for microfilariae in the peripheral blood. A direct examination of the
blood in a wet mount with 1-2 drops is a quick, easy method of doing this. However, this
type of test is relatively insensitive, and microfilariae cannot be examined morphologically.

Knott technique and filtration methods (Difil-test) are quick, easy, sensitive and allow
morphological examination.

ELISA tests, utilises a monoclonal antibody to detect circulating worm antigens.
Treatment
Adulticidal
Melarsomine dihydrochloride (Immiticide) given intramuscularly (lumbar muscles)
AHS recommends use of doxycycline and a macrocyclic lactone prior to the three-dose regimen of
melarsomine (one injection of 2.5 mg/kg body weight followed at least one
month later by two injections of the same dose 24 hours apart) for treatment of heartworm disease
in both symptomatic and asymptomatic dogs. Any method utilising only macrocyclic lactones as a
slow-kill adulticide is not recommended.
Microfilaricidal
Ivermectin (not approved as a microfilaricide) not earlier than 3-4 weeks after adulticide treatment.
It can be given subcutaneously or orally. CNS side effects are described in rough coated collies (and
other pure breeds) with high doses of Ivermectin
Milbemycin oxime (500-999mcg/kg)
Selamectin (Stronghold)
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Careful observation is required after the initial dose (potential systemic side effects).
Chemoprophylactic
for any animal that could potentially become infected.
Macrolide endectocides:
ivermectin (Heartguard 6-12 mcg/kg)
milbemycin oxime (Interceptor 500-999 mcg/kg).
selamectin (Stronghold)
Further reading
Willesen JL et al. Efficacy and safety of imidacloprid/ moxidectin spot-on solution and fenbendazole
in the treatment of dogs naturally infected with Angiostrongylus vasorum. Veterinary Parasitology
147 (2007): S. 258–264.
Ferasin L (2004) Disease risks for the travelling pet: heartworm disease. In Practice 26 (7) 350-357
Veterinary Resources at www.heartwormsociety.org
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PERICARDIAL DISEASE
Introduction
Pericardial disease is not common but its pathophysiology is unique and this demands a therapeutic
approach that differs from that of more common forms of heart disease. Furthermore, unlike many
more common cardiac disorders, pericardial disease is occasionally curable which emphasizes the
importance of its recognition.
The parietal pericardium consists of an outer fibrous layer and an inner serosal layer. The visceral
pericardium, or epicardium, is a reflection of the serosal surface of the parietal pericardium. The
pericardial cavity between the parietal and visceral pericardia is a potential space. In healthy
individuals, it contains a small volume of serous transudate. The normal pericardium appears to fulfil
only a minor role in cardiovascular function and its congenital absence is clinically silent. However,
disease of the pericardium impairs cardiac filling and this can lead to marked cardiovascular
compromise. Congenital abnormalities of the pericardium are relatively uncommon. Effusive
pericardial disease is the most common pericardial condition observed in small animal practice; it is
defined by the accumulation of an abnormally great volume of fluid within the pericardial space.
Constrictive pericardial disease is less common but it can be occasionally seen in our patients.
Pericardial constriction usually results from fibrosis of the parietal or visceral pericardium which
limits ventricular expansion and therefore impairs ventricular filling. Pericardial disease is observed
in both dogs and cats but is seldom the cause of clinical signs in the latter.
In dogs, pericardial effusion (PE) usually is hemorrhagic; numerous causes have been reported but
most commonly, canine PE is due to intrapericardial neoplasia or idiopathic pericarditis. The
prevalence of neoplastic effusion is higher than the prevalence of idiopathic PE in the United States
but there seems to be an inverted ratio in Europe. Right atrial haemangiosarcoma (HSA) and
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chemodectoma are the most common cardiac neoplasms but mesothelioma, ectopic thyroid
carcinoma, rhabdomyosarcoma and metastatic neoplasms occasionally cause PE. Infective
pericardial disease is rare and often associated with penetrating or migrating foreign bodies.
Uraemia, anti-coagulants (i.e. warfarin), trauma, idiopathic myocarditis, etc represent rare causes of
pericardial effusion.
Pathophysiology of Cardiac Tamponade
The consequences of pericardial effusion (PE) depend on the volume of pericardial fluid and on the
rate at which it accumulates. Acutely, the pericardium is minimally distensible. Therefore, when PE
accumulates rapidly, relatively small volumes cause intrapericardial pressures (IPP) to rise resulting
in impaired ventricular filling and hemodynamic compromise. In contrast, the pericardium can
stretch to accommodate an effusion that develops slowly and large volumes of fluid may accumulate
before IPP impairs cardiac filling. The syndrome of cardiac compression that results from
accumulation of pericardial fluid is known as cardiac tamponade. Right atrial and ventricular
pressures normally are lower than corresponding pressures of the left atrium and ventricle; because
of this, the right side of the heart is affected initially by tamponade. Progressive increases in
intrapericardial pressure cause equalization of left and right ventricular filling pressures after which
further increases in IPP cause ventricular filling pressures to rise in tandem. The increase in
ventricular filling pressures causes venous pressures to increase, and when PE is chronic, signs of
systemic congestion including ascites and pleural effusion are observed. Severe tamponade reduces
stroke volume and results in systemic hypotension. When pericardial fluid accumulates rapidly,
clinical signs of diminished peripheral perfusion usually dominate the clinical presentation. Signs of
systemic congestion generally develop at venous pressures that are lower than those that cause
pulmonary congestion. Most veterinary patients with PE are therefore presented for evaluation of
signs such as ascites. Pulmonary oedema is uncommon in the setting of tamponade.
Pericardial effusion and tamponade enhance ventricular interdependence potentially resulting in
pulsus paradoxus. Pulsus paradoxus is an exaggeration of physiologic changes in cardiac loading that
normally result from respiratory-associated variations in intrathoracic pressure. With respect to
acute forces, the fibrous pericardium can be considered inelastic and therefore, the total volume of
the pericardium does not vary in the short-term. During inspiration, intrathoracic pressure falls and
this augments right ventricular filling. Because the total volume of the pericardium is fixed, the
increase in right ventricular volume occurs at the expense of left ventricular filling and stroke
volume. The result is a decrease in the strength of the arterial pulse during inspiration.
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Clinical Presentation
PE develops most commonly in large-breed dogs including German shepherd dogs and retrievers.
Often, PE develops relatively slowly and patients are presented for evaluation of signs of right-sided
congestive heart failure. Abdominal distension due to ascites or dyspnea related to concurrent
pleural effusion may be observed and occasionally peripheral oedema is evident. Signs of low cardiac
output including weakness and syncope may also prompt veterinary evaluation and non-specific
signs including inappetance, depression and lethargy are common. Patients that acutely develop
severe tamponade are presented recumbent in circulatory collapse.
The physical findings of cardiac tamponade are relatively distinctive. The heart sounds usually are
muffled by the presence PE.
Tachycardia is typically present and the arterial pulse may be weak. Pulsus paradoxus is occasionally
detectable; this finding is virtually pathognomonic for the presence of cardiac tamponade. When
tamponade is present, the jugular veins typically are distended and ascites is often present when PE
is chronic.
Radiography
When large volumes of PE accumulate, the cardiac silhouette is enlarged and the contours of the
cardiac silhouette are lost so that cardiac shadow has a globose appearance. Often, the pulmonary
vessels are small. Pulmonary oedema is uncommon in the setting of tamponade.
Electrocardiography
Tachycardia is usually present when patients develop tamponade. Most often, the rhythm is sinus
tachycardia; pathologic tachyarrhythmia such as ventricular premature complexes and ventricular
tachycardia are relatively uncommon in tamponade. When the volume of PE is large, the amplitude
of the QRS complexes may be markedly diminished. Occasionally, the QRS amplitude varies in a
consistent alternating fashion known as electrical (or QRS) alternans. These electrocardiographic
findings are not present in every case; however, when QRS alternans and small complexes
accompany typical physical findings, they are highly suggestive of the diagnosis of PE.
Echocardiography
Echocardiography is invaluable in the diagnostic evaluation of patients with pericardial disease. It is
the most sensitive and specific noninvasive means by which to detect PE. Of equal importance,
echocardiography demonstrates the cause of effusion when intrapericardial masses are identified.
Echocardiography is not essential for the diagnosis of PE and tamponade; however,
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echocardiography should be considered in all cases of suspected pericardial disease because it is the
diagnostic test that is most likely to provide an etiologic diagnosis. Although two-dimensional
echocardiography is a highly sensitive method for detection of PE, the sensitivity of 2DE for
identification of cardiac masses has not been prospectively evaluated. Based on retrospective
studies, the sensitivity of 2DE for detection of cardiac neoplasia is between 17 and 68%.When
multiple imaging planes are evaluated using current echocardiographic technology, it is reasonable
to suppose that the true figure is close to, or perhaps greater, than the upper limit of this range.
Characteristics of the Effusion
Most pericardial effusions in dogs result either from neoplasia or from idiopathic pericarditis. The
prognosis associated with idiopathic pericarditis is better than that associated with neoplasia and
therefore, antemortem distinction between the two disease processes is important. Ideally, the two
causes could be distinguished by minimally invasive techniques but unfortunately a reliable means
to do so is lacking. Cytologic evaluation of PE is rarely informative 2 probably because almost all PE
in dogs are hemorrhagic and the tumours that are most commonly responsible exfoliate poorly.
Effusions related to cardiac lymphosarcoma or infection are exceptions to this but these conditions
are uncommon. It has been suggested that that idiopathic pericarditis results in an effusion that is
relatively acidic. However, other evaluations of effusion pH have failed to demonstrate the
diagnostic value of this measurement. Despite statistically significant differences between
biochemical and hematologic variables measured in neoplastic and non-neoplastic effusions, neither
haematocrit nor concentrations of analytes such as lactate, chloride and urea nitrogen usefully
discriminate between the two basic disease processes. Recent evidence suggests that there might be
a diagnostic role for determination of troponin-I; serum concentration of this biomarker is greater in
dogs with cardiac HSA than in dogs with idiopathic pericarditis.15 Despite this encouraging finding,
the non-invasive etiologic diagnosis of PE generally is made by echocardiography and clinical course.
Therapy
Pericardiocentesis is the appropriate initial therapy for patients with cardiac tamponade. The
procedure is generally performed from the right hemithorax after aseptic preparation of the site. A
14 or 16 G over-the-needle catheter is introduced into the pericardial space, the needle is removed
and fluid is withdrawn. A short pause after removal of the first 3-5 ml allows time to determine
whether or not the fluid will clot. If the aspirated fluid clots, it is possible that the catheter is within
the right ventricle.
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Monitoring of the electrocardiogram during the procedure is suggested. The procedure can be
performed blindly although some prefer to puncture the pericardium using echocardiographic
guidance. Complications are relatively uncommon and the risk:benefit ratio is decidedly in favour of
performing the procedure when tamponade is present.
It should be recognized that the vast majority of canine PE are hemorrhagic. Diuretic agents are
unlikely to mobilize the effusion but are likely to decrease venous pressures and cardiac output. For
this reason, diuretics are contraindicated in the setting of tamponade. If pericardiocentesis must be
delayed, intravenous fluid infusion is the appropriate supportive treatment. Surgical exploration
after pericardiocentesis can be considered when echocardiography demonstrates an intrapericardial
mass. In cases in which a mass is detected, it is useful to consider the presumptive histological
diagnosis. Masses that originate from the right atrium or right atrial appendage are usually HSA
while chemodectomas generally arise from the proximal aorta. Surgical debulking and adjuvant
chemotherapy may improve survival of patients with cardiac HAS.16 However, it should be
recognized that this neoplasm is associated with a poor prognosis and survival after diagnosis is
generally less than 8 months regardless of therapy. Patients with chemodectoma fare better and
median survival of 730 days after pericardiectomy has been reported. Approximately 50 % of
idiopathic PE resolves after a single centesis. Although it has been suggested that repeated centeses
might carry a more favourable risk:benefit ratio, surgical exploration and pericardiectomy should be
considered when apparently idiopathic PE recurs after two or three centeses. Surgical exploration
provides a definitive diagnosis and when idiopathic pericarditis is confirmed, pericardiectomy is
potentially curative. Subtotal pericardiectomy traditionally has been performed after a median
sternotomy or lateral thoracotomy. More recently, minimally invasive techniques for
pericardiectomy or pericardiotomy have been developed. Thoracoscopic subtotal pericardiectomy
has been reported and this technique is apt to result in lower patient morbidity relative to
thoracotomy. Balloon pericardiotomy is a minimally invasive technique in which a catheter of the
type used for balloon dilation of outflow tract obstructions is used to create a rent in the
pericardium and therefore prevent recurrence of tamponade. This procedure may have a favorable
cost:benefit ratio particularly as a palliative procedure for patients with neoplastic effusion.
Prognosis
The prognosis associated with effusive pericardial disease is largely determined by the etiology of
the effusion. In general, patients with cardiac HSA have a poor prognosis. The prognosis after
pericardiectomy for patients with chemodectoma may be surprisingly good presumably because the
tumours grow relatively slowly and are late to metastasize. Although prolonged survival has been
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documented, patients with pericardial mesothelioma generally fare poorly and have decreased
survival relative to dogs with idiopathic PE. Patients with idiopathic pericardial effusion have a good
or excellent prognosis. A few clinical findings provide prognostically useful information. Patients that
have ascites when first presented for veterinary evaluation live longer than those that do not.
Presumably this is because patients with aggressive, hemorrhagic tumours such as HSA are more apt
to develop signs associated with circulatory collapse than signs of congestion. Independent of
histological findings, the prognosis is generally poor for patients with an echocardiographically
identified mass that originates from the right atrium.
CONSTRICTIVE PERICARDITIS
Constrictive pericarditis is an uncommon disease that impairs diastolic function.22 Ventricular filling
is impeded due to pericardial constriction that is due to pericardial fibrosis. Clinical signs are
generally related to systemic congestion and low cardiac output. The disease is a diagnostic
challenge; cardiac catheterization studies are generally required. Surgical treatment consists of
pericardial stripping.
Further Reading
Jonathan A. Abbott, Pericardial disease – diagnosis and therapy, ACVIM forum proceedings,
Louisville, Kentucky, 2006
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SYNCOPE, FALLING, SEIZURES
Introduction
Episodic collapse, recurrent syncope, intermittent weakness and seizures are common complaints in
canine and feline medicine.
The term “collapse” derives from the Latin word collapsus, past participle of collabi, meaning “to fall
apart”. In human medicine, the term collapse defines “a state of extreme prostration and
depression” or “a falling together of the walls of a structure” or “the failure of a physiologic system”.
The word collapse is not even mentioned in the Merck’s manual of medicine. Therefore, for a pure
semantic convention, we should probably reserve the word collapse to define conditions like
“tracheal collapse” or “profound hypotension” and use the simple term “fall” to describe a loss of
quadrupedal posture.
Animals may fall as a consequence of:
1.
cerebral hypoperfusion (syncope)
2.
abnormal electrical activity of the brain (seizure)
3.
weakness
4.
cramps
5.
pain
Most cases of episodic fall occur during exercise, even in healthy young and fit individuals.
Syncope
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The word syncope derives from ancient Greek synkopē, meaning “cut off”. It describes a sudden,
unexpected, and unprovoked loss of consciousness. The affected subject loses postural control and
remains unresponsive throughout the event. It is a transient condition which lasts for only a few
seconds and it is always followed by spontaneous and complete recovery. This obviously differs from
“sudden death”, which could be defined as an “irreversible syncope”. Therefore, the only difference
between syncope and sudden death is that in one you wake up. The underlying mechanism is a
transient global cerebral hypoperfusion4. Lipothymia (or pre-syncope) is a condition in which
patients experience warning symptoms telling them they are about to pass out. This allows patients
to "prepare" for collapse without bodily harm (laying on the sofa).
In people, irrespective of the precise underlying cause of syncope, a sudden cessation of cerebral
blood flow for 6–8 s and/or a decrease in systolic blood pressure to 60 mm Hg has been shown to be
sufficient to cause complete loss of consciousness4. Critical physiological values that can induce
syncope in dogs and cats are not available but it is not unrealistic to believe that they may be similar
to those reported in people. Causes of syncope are primarily cardiovascular, although some noncardiovascular conditions need to be considered in the differential diagnosis. A summary of potential
causes of syncope is reported in the table below.
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Cardiac
Non-Cardiovascular
Anatomical outflow obstruction (severe SAS o PS, heart
Neurological (seizure disorder, head
base or intracardiac tumours)
trauma, hepatic encephalopathy,
narcolepsy, Scottie cramp, episodic
falling in CKCS, autonomic
neuropathy)
Cardiac tamponade (pericardial effusion)
Obstructive HCM
Metabolic (hypoglycaemia)
Myocardial ischemia
Bradycardia (high degree AV block, Atrial standstill, sick
Psychological (anxiety, panic,
sinus syndrome, asystole)
somatisation disorders)
Tachycardia (SVT, VT)
Iatrogenic (ACP, hydralazine,
amlodipine, nitrates, etc)
Vascular
Orthostatic hypotension (venous pooling = frequent in
Miscellaneous (e.g. pacemaker failure)
people)
Pulmonary thromboembolism
Pulmonary hypertension
Neurocardiogenic (vasovagal)
Hypovolaemia/ dehydration
Situational (straining during coughing, defecation,
micturition, swallowing)
With the exception of the American opossums, which are renowned for "playing dead" when
threatened, psychological syncope is not commonly described in veterinary medicine. Iatrogenic
arterial dilation may occur after administration of drugs that induce vasodilation, such as
nitroprusside, acepromazine, or amlodipine. All the abnormalities listed above can potentially induce
cerebral hypoperfusion and ultimately loss of consciousness. However, some animals may fall,
appear weak or present signs of pre-syncope when they experience milder events.
Seizure
The word seizure derives from the ancient German “sezzen’ (to set) and indicates a temporary
abnormal electrical activity of the brain, resulting in altered mental state and uncontrolled muscular
activity (fit or convulsions). A seizure can last from a few seconds to a prolonged status epilepticus.
The medical syndrome of recurrent, unprovoked seizures is termed epilepsy. However, seizures may
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also occur in patients that do not have epilepsy. Hepatic encephalopathy, narcolepsy, Scottie cramp,
episodic falling in CKCS are some examples frequently observed in veterinary medicine5. Some cases
of partial seizures can mimic syncope. Similarly, some cases of prolonged cerebral hypoperfusion can
present with seizure-like activity.
Weakness
The word “weak” derives from the ancient Greek “eikein’ (to give way). It is defined as a loss of
muscular strength resulting in an animal becoming completely or partially recumbent or ataxic.
Generalised muscle weakness is referred to as asthenia. Weakness during exercise can be
physiological (exhaustion). However, it can also be caused by a variety of clinical abnormalities, such
as muscular (myopathy), neuro-muscular (myasthenia), neurological, metabolic (electrolyte
imbalance, hypoglycaemia), haematological (anaemia, polycytaemia), and cardiovascular
(arrhythmias, forward heart failure, right-to-left PDA) conditions.
Muscle Cramps
The word cramp derives from ancient German “krampf” meaning “squeezing, pressing, or pinching
uncomfortably”. It is a sudden, uncomfortable, contraction of a muscle, lasting seconds to minutes,
often with a palpable hard knot in the affected muscle. Stretching the muscle or contraction of its
antagonist muscle often relieves the cramp. On electromyogram (EMG), the involuntary muscle
contraction is associated with repetitive firing of motor unit action potentials at high rates (up to 150
per second). In people, the significance of cramps ranges from a benign, infrequent muscle pain to
one of the symptoms heralding a devastating neurological disease such as amyotrophic lateral
sclerosis (ALS). Muscle cramps have also been described in athletic dogs8 and in dogs with
hypoadrenocorticism or hypothyroidism. However, cramps are rarely reported as a complaint in
small animal practice.
Pain
Muscle pain (myalgia) or pain originating from the spinal or appendicular musculo-skeletal system
can cause fall, especially during exercise. A sudden, intermittent and painful recumbency in cats can
be the result of a partial arterial occlusion caused by arterial thromboembolism (ATE).
Clinical investigation of episodic falls
The transitory nature of episodes and spontaneous resolution of clinical signs represent a real
diagnostic challenge. In people, when there are not abnormalities detected on history or clinical
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examination, diagnosis may not be achieved in approximately 50% of cases. Similar figures are
reported in small animal practice.
An excellent understanding of the efficacy and utility of the investigational tools for syncope is
therefore required in order to institute promptly and efficiently an appropriate management. In fact,
a wrong choice of sequential tests may result in poor diagnostic yield and unnecessary costs. Finally,
a delayed diagnosis may result in sudden death.
History and physical examination
A thorough and consistent history, followed by a full physical examination, is the most important
component of the evaluation of a patient with episodic fall.
Every effort should be made to differentiate between true syncope with loss of consciousness from
apparent syncope, although an overlap between the two may exist. In the history interview, we
should always evaluate:
1.
History of cardiac disease or medications that may induce arrhythmias or hypotension
2.
Number and frequency of the episodes in full details
3.
Identifying precipitating factors, including detailed description of physical activity, time of
the day, environmental conditions, degree of excitement, etc.
4.
Quantifying type and duration of the event, including prodromal and recovery period.
5.
Obtain information about colour of mucous membranes and heart beat during phases
6.
Obtain careful accounts of witnesses who may have been present and, when possible,
acquire a video recording of the event
Clinical history of arrhythmia (both brady- and tachy-arrhythmias) are similar. In both cases syncope
occurs after approximately 5 seconds of warning, lasts for a few seconds and recovery is very rapid
and uneventful. Arrhythmia should always be suspected in case of predisposed breeds like Boxers
(ARVC), Dobermans (occult DCM) and German shepherd puppies (GSD inherited VT). Disorientation
and behavioural changes following the event, absence of pale or cyanotic mucous membranes,
frothing at the mouth, aching muscles, lethargy after the event, and unconsciousness lasting for
more than a few minutes would suggest seizure rather than syncope. Although urination and/or
defecation can occur during syncope, this is more commonly associated with a seizure. Gran mal
seizures are commonly associated with tonic-clonic movements, while syncope is often
characterised by a flaccid paralysis of the limbs. However, syncope caused by cerebral ischemia can
result in decorticate rigidity, with clonic movements of the limbs. Akinetic or petit mal seizures are
often characterised by lack of responsiveness in the absence of a loss of postural tone.
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Physical examination should be conducted in a thorough and consistent manner. Particular attention
should be paid at the examination of the cardiovascular system (including blood pressure
measurement), level of hydration, and presence of significant neurological or musculoskeletal
abnormalities. Pre-organized questionnaires and checklists will tremendously assist the clinician in
obtaining valid information in an efficient and standardised manner.
In human patients with recurrent falls, blood tests (basic haematology and serum biochemistry) have
a low diagnostic value and the tilt-table represent the first line test. However, orthostatic syncope in
small animals is unlikely and tilt-table testing is inapplicable. Echocardiography should be considered
in case of abnormal findings during physical exam (i.e. heart murmur, arrhythmia, etc) or in case of
familial history/predisposition of cardiac disease.
Resting ECG may identify the reason of fall in a small percentage of patients. However, the
diagnostic power of ECG increases dramatically if it is recorded during exercise via radio-telemetry,
especially in cases of exercise-induced falls. Twenty-four hour (Holter) ECG recording has a very low
diagnostic value, especially when the falling episodes occur sporadically. The only exception for
justifying Holter analysis in these cases is for the breed-related predispositions mentioned above.
Conversely, event recorders can provide a diagnostic yield in approximately 25% of the patients and
the figure increases dramatically (47%) if an implantable recorder (ILR) is used.
Recently, the reliability and accuracy of an implantable loop recorder has been reported in the
veterinary literature with excellent results described both in dogs and cats. These studies show that
in dogs and cats with unexplained syncopal episodes, the manually activated ILR can provide
invaluable diagnostic and prognostic information in almost all patients, by either confirming or
disproving the association between syncope and arrhythmias.
Other investigations (e.g radiology, abdominal US, CT scan, MRI, EM, EEG, etc.) might be
recommended in case all the tests listed above result inconclusive.
In the last few years, I have tried to design a diagnostic algorithm in an attempt to increase the
diagnostic ratio in cases of episodic fall. This algorithm is continuously revised following the
availability of new diagnostic tests and the increasing personal experience in this field. However,
case reports and discussion with colleagues are strongly encouraged in order to achieve a more
successful and cost/time-efficient diagnostic approach to these extremely challenging cases.
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EXERCISE INDUCED COLLAPSE (EIC) IN LABRADOR RETRIEVERS
Introduction
Exercise induced collapse (EIC) is a term that describes a form of exercise intolerance seen in young
Labrador retrievers after strenuous exercise. Although the first report of EIC dates back to 1993, the
first citation in the veterinary literature is very recent (2008). According to the authors, affected dogs
sometimes develop an abnormal gait or collapse when subjected to strenuous exercise, but the
underlying cause has not been well established. Affected dogs usually tolerate mild-moderate
exercise but occasionally become ataxic and collapse after 5 to 15 minutes of intense exercise,
especially when accompanied by excessive excitement or stress.
The pattern of the clinical signs (described by the aforementioned authors as “collapse”) is poorly
characterised, as demonstrated in a survey carried out by 225 owners of dogs with a history of EIC
(table 1)
Table 1 Owner description of clinical signs 17
Description
% of dogs
Rear limbs floppy/dragged
78
Wobbly, uncoordinated
60
Falling to side/ balance problem ≥1 episode
68
Rear limbs only affected
82
All four limbs affected ≥1 episode
18
Forelimb rigidity ≥1 episode
18
Dazed/disoriented ≥1 episode
23
Loud/excessive panting ≥1 episode
19
Generalised seizure during 1 episode
3
The physical activity that appears to trigger the event is also poorly defined and includes retrieving
toys (46%), retrieval training on land (43%), upland hunting (25%), excitement during play with other
dogs (22%), retrieval training in water (12%) and waterfowl hunting (2%).
Some factors seem to contribute to the onset and development of clinical signs, including
excitement (83%), heat and humidity (31%), use of live birds in training or hunting (25%), stress
during training (13%) and competition with other dogs (9%).
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In the examination of the pedigree of 326 dogs, 169 individuals appeared to be affected, with nine of
these appearing to have an affected parent. Males and females were equally represented, excluding
an X-linked mode of inheritance. Six of the nine affected parents had full phenotypic information.
One affected parent mated with another affected parent producing two affected and two
unaffected offspring. In three families, an affected dog produced multiple affected second and third
generation offspring. The pedigree analysis was most consistent with an autosomal recessive mode
of inheritance, although a dominant disorder with partial penetrance or a polygenic disorder could
not be excluded.
Median age of dogs when they presented the first episode of collapse was 12 months. 10% of dogs
had experienced more than 25 episodes of collapse and seven had died during a collapsing episode.
Three of these individuals had generalised seizure just before death. However, the authors do not
report whether or not these dogs underwent a cardio-vascular investigation to rule out, for example,
episodic arrhythmias or a right-to-left shunting persistent ductus arteriosus (reversed PDA).
Although the authors failed to report in their first paper that most EIC dogs will experience
spontaneous resolution of the clinical signs and will not show any further collapsing episodes during
adult life, in a most recent publication they state: “Five years have passed since the 14 dogs with EIC
were evaluated. One dog was euthanized immediately following evaluation. Six dogs were adopted
out to pet homes where they no longer participate in the trigger activities associated with the
collapse, and five dogs have not collapsed since relocation. Three dogs remained with their owners
and episodes of collapse reportedly occur if they are allowed to engage in trigger activities. One dog
has not had activity limited, but episodes of collapse have become very infrequent. Three dogs were
lost on follow-up. No dogs have developed progressive systemic or neurological disorders and all are
considered by their owners to be healthy aside from the EIC”.
The mechanism of EIC has not been determined yet, although “a mutation in dynamin 1 gene
(DNM1) was recently suggested as the causal mutation of EIC in Labrador retrievers. A genetic test
for the mutation is now available through the Veterinary Diagnostic Laboratory at the University of
Minnesota”. Regrettably, the conflict of interest was not disclosed in the above manuscript despite
the fact that authors share royalties for the test.
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The DNM1 mutation has been described in an elegant study published in 2008 by the same research
group.19 In this study, the authors used a genome-wide scanning technique on six pedigrees of
Labrador retrievers in which EIC was segregating and they identified a locus at the 60.4 Mb position
of canine chromosome 9 (CFA9) with significant linkage. They subsequently analysed SNP markers
from the region for association with EIC using 310 Labrador retrievers and found multiple associated
markers. After further stratification of the population, they identified three significantly associated
SNPs in a 355-kb region (58.519–58.874 Mb). The most common haplotype in EIC dogs extended
nearly the entire 4.5-Mb segment for which SNPs were analysed and homozygosity was observed for
a minimum of 929 kb in 89% of these dogs. Homozygosity in 10% of the affected dogs was, however,
limited to two short haplotype blocks: a 137-kb block and an 87-kb block, separated by a 184-kb gap
(Fig. 2a). These two haplotype blocks were also observed in the unaffected dogs, as would be
expected from their unavoidably close relationships to the affected dogs.
The major criticism about the above discoveries is about the arbitrary stratification operated by the
authors to achieve a significant association. Dogs were divided into six groups (presumed EIC,
recurrent collapse, single collapse, atypical collapse, alternative collapse, and no collapse). Further
arbitrary selection is observed in the alternative collapse group where “other potential causes of
repeated collapse” were listed, such as cardiac arrhythmia, laryngeal paralysis, lactic acidaemia, and
metabolic myopathy. Moreover, 9% of dogs without a history of collapse resulted homozygous for
the mutation, which was explained by the owners as insufficient exercise or excitement to trigger
collapse. Finally, if the cause of collapse was really induced by insufficient vesicles for sustained
synaptic transmission and subsequent reversible loss of motor function, why do clinical signs not
present at all times? What is the real threshold or cut-off limit? Have the authors proved the lack of
synaptic transmission?
The major problem in the study of this condition originates from the lack of objective parameters to
assess the physical condition of these dogs. It is well known that exercise causes significant acute
alterations in rectal temperature (BT), pulse rate (HR), blood lactate (BL) and other physiological
parameters in healthy dogs.20-23 However, until recently, there were no available data originating
from standardised studies where test–retest reliability has been assessed.
In our recent publication, Dr Marcora and I assessed the reproducibility of a non-invasive exercise
test in healthy Labrador retrievers and evaluated BL, HR and BT responses that occur during and
after incremental exercise in this breed. In this study, we demonstrated that differences between
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tests may exist even under the strictest controlled conditions, such as environmental temperature,
humidity, intensity of exercise, diet, time of the day, etc. Therefore, the standardised field tests
conducted by other groups present several limitations, with little scientific accuracy and clinical
utility.
Another important finding in our study was a prolonged recumbency and temporary inability to
regain the quadrupedal posture in most dogs during the recovery period. This resembled the typical
features of exercise-induced collapse described by Taylor et al. We interpreted these signs as an
extreme physiological condition (exertional fatigue or exhaustion). This could be attributed to a
variety of reasons. Exercise-induced changes in muscle action potential, extracellular and
intracellular ions, and intracellular metabolites reduce the ability to produce force (peripheral
fatigue). Changes at spinal and supraspinal level due to alterations in brain metabolism and
neurotransmitters, or inhibitory afferent feedback from type III and IV muscle afferents can also
reduce the ability of the CNS to activate the locomotor muscles (central fatigue). It is also possible
that, in these dogs, the increased pulmonary blood flow and capillary pressure during intense
exercise induced the activation of pulmonary C fibers (or J receptors). This activation can evoke a
somatomotor reflex (the J reflex) that provides potent inhibition of limb muscles in animals but not
humans. In contrast with what has been observed in people, incremental exercise did not appear to
induce abrupt increases in BL concentration in Labrador retrievers, although significant variation was
observed between test stages. Moreover, in humans, BL concentrations would be expected to
decrease during recovery after intense exercise. However, in our study, BL values remained stable
after a 20-min recovery period in all dogs. Blood lactate concentration during exercise is the result of
lactate production by the contracting muscle, lactate transport from the muscle to the vascular bed,
as well as intracellular and hepatic clearance. Assuming that lactate clearance would continue during
recovery and that lactate production in the muscle would cease after termination of the exercise, it
can be speculated that the modest increase of lactate values observed in Labradors depends on a
slow transport of this compound from muscle to blood. This could be caused by a low muscular
density of proteins involved in lactate transport (i.e., monocarboxylate transporter or MCT) and/or
intracellular lactate clearance.
According to the EIC test patent owners, breeders need to be selective in their breeding, avoiding
the production of dogs that actually have EIC. They advise that all breeding dogs should be tested,
and if carrier dogs are bred they should only be bred to dogs that are genetically clear of EIC so that
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affected puppies will not be produced. They also advocate avoidance of intensive exercise and, in
some cases, the use of phenobarbital to decrease the dog’s level of excitement or anxiety.
I kindly (and strongly) disagree with the above approach. I have now managed to successfully treat
dozens of Labrador (and non Labrador) dogs with a history of EIC. First of all, it is necessary to rule
out an underlying cardiac abnormality with a full cardiac work-up, including full echo-colour Doppler
and 24h Holter ECG monitoring. Afterwards, the exercise capacity should be assessed on a validated
treadmill test to obtain baseline values of BL, HR and BT. A field test would offer limited value due to
its poor repeatability. Finally, a well-designed exercise prescription, primarily based on interval
training, is normally sufficient to improve the physical ability of the dog to undergo intense training.
The exercise prescription can be designed based on the results of the exercise test. It is mandatory
to maintain a good communication with the dog’s owners and make sure that the prescribed
exercise is recorded on a diary. Finally, owners’ expectations need to be carefully evaluated.
Sometimes, owners force their dogs to undergo exhausting exercise even several times a day. Under
these circumstances, young excitable dogs are at higher risk of “collapse” because they tend to
exercise above their physical capacity.
Further reading
Stedman TL. Stedman's medical dictionary, 28th ed. ed. Philadelphia, Pa. ; London: Lippincott
Williams & Wilkins; 2006;1 v. (various pagings).
Beers MH. The Merck manual of medical information, 2nd home ed. ed. Whitehouse Station, N.J.:
Merck Research Laboratories; 2003;xxxviii, 1907 p.
Engel GL. Psychologic stress, vasodepressor (vasovagal) syncope, and sudden death. Ann Intern Med
1978;89:403-412.
Brignole M. Distinguishing syncopal from non-syncopal causes of fall in older people. Age Ageing
2006;35 Suppl 2:ii46-ii50.
Martin MWS, Corcoran BM, Martin MWSCdotd, et al. Notes on cardiorespiratory diseases of the dog
and cat, 2nd ed. ed. Oxford: Blackwell Publishing; 2006;x, 205 p.
Zaidi A, Clough P, Cooper P, et al. Misdiagnosis of epilepsy: many seizure-like attacks have a
cardiovascular cause. J Am Coll Cardiol 2000;36:181-184.
Miller TM, Layzer RB. Muscle cramps. Muscle Nerve 2005;32:431-442.
Shadan S. Genetics: run, whippet, run. Nature 2007;447:275.
Saito M, Olby NJ, Obledo L, et al. Muscle cramps in two standard poodles with hypoadrenocorticism.
J Am Anim Hosp Assoc 2002;38:437-443.
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Shelton GD. Muscle pain, cramps and hypertonicity. Vet Clin North Am Small Anim Pract
2004;34:1483-1496.
Gould PA, Krahn AD, Klein GJ, et al. Investigating syncope: a review. Curr Opin Cardiol 2006;21:34-41.
Willis R, McLeod K, Cusack J, et al. Use of an implantable loop recorder to investigate syncope in a
cat. J Small Anim Pract 2003;44:181-183.
Libby P, Braunwald E. Braunwald's heart disease : a textbook of cardiovascular medicine, 8th ed. ed.
Philadelphia, Pa. ; Edinburgh: Elsevier Saunders; 2008;1 v. (various pagings).
Ferasin L. Recurrent syncope associated with paroxysmal supraventricular tachycardia in a Devon
Rex cat diagnosed by implantable loop recorder. J Feline Med Surg 2009;11:149-152.
James R, Summerfield N, Loureiro J, et al. Implantable loop recorders: a viable diagnostic tool in
veterinary medicine. J Small Anim Pract 2008;49:564-570.
Santilli RA, Ferasin L, Voghera SG, et al. Evaluation of the diagnostic value of an implantable loop
recorder in dogs with unexplained syncope. J Am Vet Med Assoc 2010;236:78-82.
Taylor SM, Shmon CL, Shelton GD, et al. Exercise-induced collapse of Labrador retrievers: survey
results and preliminary investigation of heritability. J Am Anim Hosp Assoc 2008;44:295-301.
Taylor SM, Shmon CL, Adams VJ, et al. Evaluations of labrador retrievers with exercise-induced
collapse, including response to a standardized strenuous exercise protocol. J Am Anim Hosp Assoc
2009;45:3-13.
Patterson EE, Minor KM, Tchernatynskaia AV, et al. A canine DNM1 mutation is highly associated
with the syndrome of exercise-induced collapse. Nat Genet 2008;40:1235-1239.
Hinchcliff KW, Olson J, Crusberg C, et al. Serum biochemical changes in dogs competing in a longdistance sled race. J Am Vet Med Assoc 1993;202:401-405.
Ilkiw JE, Davis PE, Church DB. Hematologic, biochemical, blood-gas, and acid-base values in
greyhounds before and after exercise. Am J Vet Res 1989;50:583-586.
Matwichuk CL, Taylor S, Shmon CL, et al. Changes in rectal temperature and hematologic,
biochemical, blood gas, and acid-base values in healthy Labrador Retrievers before and after
strenuous exercise. Am J Vet Res 1999;60:88-92.
Steiss J, Ahmad HA, Cooper P, et al. Physiologic responses in healthy Labrador Retrievers during field
trial training and competition. J Vet Intern Med 2004;18:147-151.
Ferasin L, Marcora S. Reliability of an incremental exercise test to evaluate acute blood lactate, heart
rate and body temperature responses in Labrador retrievers. J Comp Physiol B 2009;179:839-845.
Matwichuk CL, Taylor S, Shmon CL, et al. Changes in rectal temperature and hematologic,
biochemical, blood gas, and acid-base values in healthy Labrador Retrievers before and after
strenuous exercise. Am J Vet Res 1999;60:88-92.
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Steiss J, Ahmad HA, Cooper P, et al. Physiologic responses in healthy Labrador Retrievers during field
trial training and competition. J Vet Intern Med 2004;18:147-151.
Ferasin L, Marcora S. Reliability of an incremental exercise test to evaluate acute blood lactate, heart
rate and body temperature responses in Labrador retrievers. J Comp Physiol B 2009;179:839-845.
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CONGENITAL HEART DISEASE
PATENT DUCTUS ARTERIOSUS (PDA)
Introduction
The PDA is the Ductus Arteriosus that fails to close after birth and remains Patent (PDA). This
abnormality will lead to pulmonary over-circulation due to the shunting of blood from the high
pressure aorta to the low pressure pulmonary artery. Secondary left heart volume overload will
develop as a consequence of this pulmonary over-circulation. Finally the pathology will degenerate
in left congestive heart failure associated or not with pulmonary hypertension and Eisenmergher
physiology (pulmonary resistance to systemic resistance ratio equal to or greater than one).
Anatomical and functional considerations
Structurally the DA originates from the left 6th aortic arch and allows a direct communication
between the descending aorta and the pulmonary artery.
In foetal development DA allows shunting of blood from the pulmonary to the systemic circulation
since the oxygenation of blood occurs in the placenta and not in the lungs. The direction of shunt
from pulmonary to systemic circulation is a consequence of the fact that the lungs are collapsed
resulting in high pulmonary vascular resistance.
Following parturition there is a decrease in pulmonary pressure as the lung begins to ventilate. This
leads to an increase in oxygen saturation that combined with the lower prostaglandin levels causes
functional closure of the ductus, followed by anatomic obliteration during the ensuing weeks of life.
Failure of ductal closure is due to the lack of normal ductal musculature. The ductal wall in healthy
dogs is constituted predominantly (about 98%) by uniformly distributed smooth muscle throughout
the wall, mainly circumferential and contracted. The remainder tissue is made up of scattered subadventitial elastic fibres intermingled with loose collagen in the adventitia.
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Histopathology in a line of dogs derived from Miniature Poodles with hereditary PDA, consistently
identified abnormalities in the wall of the ductus arteriosus that explained failure of the ductus
closure after birth. The two main histological features observed in these cases were hypoplastic and
asymmetric ductus smooth muscle and the presence of non-contracting aorta-like elastic tissue
(segments of the ductus wall that should be muscular had instead a non-contracting, aorta-like
elastic wall). The muscular portion was always situated near the pulmonary artery and the thinner
elastic portion (aorta-like tissue) always was adjacent to the aorta.
Serial-section histology of foetuses predisposed to PDA identified 6 grades of abnormality
characterized by asymmetrically reduced smooth muscle and increased aorta-like elastic tissue that
correlated with increased PDA gene concentration in breeding experiments.
Grade 1-2
•Lack of enough muscle to close the aortic end of the duct but
presence of enough muscle to close the pulmonary artery end
resulting in a non PDA. This leaves a ductal aneurysm, a blind
diverticulum (non-patent forme fruste). This mild defect is the occult
form that it can be diagnosed only by necropsy and angiography
Grade 3-5
•Lesions result from small, medium, and large sizes ductus respectively
based on the muscle quantity that remains at the pulmonary end. The
ductal musculature is absent at the aortic end of the duct and mostly
present at the pulmonary end, with some muscle remaining along the
duct. This distribuition result in a partial closure. The less muscle
remaining at the pulmonary end the greater will be the pulmonary
end opening so the greater will be the ductus. This distribution of
muscle results in the characteristic funnel shape of the typical left-toright shunting PDA
Grade 6
•Is the most severe but the least frequent form. The ductus remains as
it was in fetal life (large shunt) because of completely no ductal
constriction. This type of ductus results in a large left-to-right shunt
that may determine perinatal death as well as will develop pulmonary
hypertension early in life (Eisenmenger´s syndrome, see in the
pathophysiology section) creating a bi-directional or right-to-left
shunt.
The ductus is widest at the aortic end and smaller at the pulmonary end being the pulmonary end
the smallest orifice in the PDA, also called PDA ostium. PDA ostium provides resistance to blood flow
and determines a pressure gradient between the aorta and pulmonary artery that can be measured
non-invasively by Doppler echocardiography.
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Genetics and Breeds
Increased prevalence of this condition has been observed in certain breeds of dogs indicating that
genetic factors were involved in the pathogenesis of PDA, and a mixed-breed–Poodle line of dogs
with hereditary PDA was developed.
It has been observed also that the heritability does not follow a simple Mendelian genetics.
PDA is one of the most common congenital heart disease.
There is a breed and sex predisposition (affecting more females than males in a ratio 2:1 or 3:1):

German Shepherd

American cocker spaniel

Collie

Pomeranian

Shetland sheepdog

Maltese

English Springer spaniel

Keeshond

Yorkshire terrier

Rottweiler
Pathophysiology
After birth, as a consequence of the higher systemic pressures compared to pulmonary pressures,
the blood shunts through the ductus from left to right during both systole and diastole. The blood
that flows from the aorta to the low pressure pulmonary circulation through the PDA, traverses the
lungs and returns to the left heart. To accommodate this increased blood return, the left ventricle
grows to a larger size. The result is an increased left ventricle end-diastolic volume, termed “volume
overload”, that compensates blood shunted through PDA from systemic to pulmonary circulation.
The increased end-diastolic volume of the left ventricle will determine an increased end-diastolic LV
wall stress which will determine an eccentric hypertrophy of the left ventricle as a compensatory
mechanism. The amount of shunting blood is dependent on the size of the smallest PDA diameter
and the relative resistances of the systemic and pulmonary circulations. The quantity of smooth
muscle will determinate the size of the ductus. Small ductus may not result in serious hemodynamic
sequelae because compensatory mechanisms may be able to accommodate mild overload.
However, in the long term, even small ductus may lead to congestive left heart failure (CHF). Large
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ductus usually overwhelms the ability of the left heart to compensate by volume overload
hypertrophy, resulting in increased left ventricular end-diastolic pressure, which frequently leads to
CHF. Depending also on the ductus size, enlargement of the proximal aorta, main pulmonary artery
and over-circulation of the pulmonary vascular bed may be seen. The right atrium and right ventricle
remain usually normal because shunting happens at the level of the great vessels. These structures
are never overloaded unless pulmonary artery pressure increases.
Bi-directional or complete reversed shunting direction (right to left) may also be found in a small
number of cases. In these cases, the lumen of PDA remains wide open after birth being the same size
as aorta and pulmonary artery, not offering resistance to blood flow. Blood flows between the aorta
and pulmonary artery without resistance and the aortic pressure is transmitted to the pulmonary
circulation and therefore, both aortic and pulmonary pressures become balanced. These patients are
not presented with left heart failure after birth probably because pulmonary vascular resistance do
not decrease to normal but remain partially elevated to prevent massive shunting. The increase in
pulmonary artery pressure combined with the increase in pulmonary blood flow causes pathologic
responses in the pulmonary arteries over time. The histological changes observed in these
pulmonary arteries include hypertrophy of the media and thickening of the intima in the medium
and small pulmonary arteries. This will determine a reduction of the lumen dimensions leading to
the pulmonary hypertension (Eisenmenger’s syndrome physiology). The exact mechanism for this
process in unknown but probably involves injury to the endothelial cells that activates growth
factors. These lesions are considered irreversible. Blood flow from the aorta to the pulmonary artery
through the ductus starts to decrease due to increase in pulmonary vascular resistance.
Consequently, the blood flow velocity decreases. When pulmonary vascular resistance is greater
than systemic vascular resistance, blood shunts from right to left and it is called reversed PDA.
A large amount of deoxygenated blood shunts from the pulmonary artery into descending aorta
producing a differential cyanosis.
Exercise result in a decrease in systemic vascular resistance producing an increase in right-to-left
shunt and exacerbation of cyanosis occur. This mechanism, together with the increased muscular O 2
demand, explain why some of these patients present episodic rear limb weakness during exercise.
The renal oxygenation is decreased leading to an increase of erythropoietin production secondary to
activation of oxygen receptors. Compensatory polycythaemia occurs and may become harmful if the
haematocrit reaches 70-75% causing increased blood viscosity and resistance to blood flow. This
compromises systemic blood flow and decreases tissue oxygen delivery. In the pulmonary
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circulation, systemic hypoxemia produces pulmonary vasoconstriction. Pulmonary vasoconstriction
combined with the increased viscosity worsen pulmonary hypertension.
Although it is a rare scenario, a dog with a common moderate-severe left-to-right shunting can
develop pulmonary hypertension and gradual reversion may occur with age. This type of pulmonary
hypertension may be due to chronic pulmonary venous congestion but the exact mechanism for this
is not completely known.
Diagnosis:
Clinical presentation
Although severely affected pups and kittens may appear stunted, thin or tachypnoeic from left heart
failure, most are reported to be asymptomatic and developing normally at the time the condition is
discovered. Clinical signs are rarely recognized within the first few weeks of life, and most dogs are
not diagnosed until the initial examination at 6 to 8 weeks of age. Some dogs that the condition has
not been recognized during the first months of life may develop congestive heart failure having a
history of coughing, dyspnoea and tachypnoea.
The hallmark of a PDA is a continuous murmur over the left 3rd intercostal space. The PMI is in the
left axillary area which means that we have to stress the auscultation (sometimes pulling forward
the arm of the dog) in order to interrogate this cranial region properly otherwise is very easy to miss
this murmur. This usually occurs if the veterinarian auscultates only over the left heart apex and
base. In some cases there is a different intensity of the murmur through the cardiac cycle increasing
the intensity throughout systole and decreasing throughout diastole but usually the murmur is truly
continuous.
The murmur may be of any intensity but is often loud (grade 4-6/6) and may radiate cranially (to the
sternum) and to the right cranial thorax. A palpable thrill can be felt in the cranial thorax, especially
in those cases with a large PDA. When the PDA is very small, the murmur may be very localized and a
thrill may not be palpable. Neonatal or older dogs with a very large left to right shunt and equalizing
diastolic pressures (low systemic or elevated pulmonary artery pressure) have only a systolic rather
than a continuous murmur. Dogs with large shunts may also have mitral regurgitation secondary to
annular dilatation with a consequent systolic murmur at the left apex. The murmur may be difficult
to be auscultated in dogs in heart failure as pulmonary crackles are predominant.
The femoral artery pulse is often increased and it is often described as a bounding or water-hammer
pulse.
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Dogs with pulmonary hypertension and bi-directional shunt or right-to-left PDA are easily missed on
physical examination because they usually have a mild systolic or no murmur at all. They may have a
split second heart sound but this is not always detectable. Occasionally they have a faint diastolic
murmur caused by pulmonic valve regurgitation.
Radiography
Radiographic abnormalities reflect the degree of cardiac volume overload, congestive heart failure
and pulmonary over-circulation. These changes depend on the size of the PDA, presence of
concomitant cardiac abnormalities and pulmonary hypertension. In mild cases it is possible to
observe only the over-circulation pattern characterized by an increased pulmonary vascular size.
However the variation in pulmonary vascular size in normal dogs sometimes makes this finding
difficult. Dogs with a relatively large left to right shunt commonly have an enlargement of the left
ventricle, left atrium and a dilated aortic arch, giving the appearance of generalized cardiomegaly
with pulmonary over-circulation, and venous prominence often evident. An increase in pulmonary
vascular size usually correlates with a significantly increased shunt volume. An aneurysmal bulge in
the descending aorta in the region of the ductus may be seen on the dorsoventral or ventrodorsal
radiograph. In cases with increased main pulmonary artery, it may be observed as a buldge at the 2o’clock position on the dorsoventral or ventrodorsal radiograph. Pulmonary venous enlargement
and pulmonary oedema may be visible in dogs with left heart failure.
Dogs with right to left shunting may present right ventricle enlargement and enlarged main
pulmonary artery with normal or diminished peripheral pulmonary vasculature.
Electrocardiography
The most common abnormality on the electrocardiogram is an increase in R wave amplitude in lead
II as a result in left ventricular enlargement. This finding is present in approximately 50% of cases
with left ventricular enlargement. Deep S waves can occur in patients with right heart hypertrophy in
patients with pulmonary hypertension.
Supraventricular and venticular arrhythmias may be present. In a recent preliminary study we have
observed an increased risk for sudden death in patients who presented ventricular arrhythmias
suggesting to be a negative survival prognostic factor. Further studies are necessary to support these
preliminary results.
Clinical PDA Classification
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Patient history and clinical features of PDA depend upon the size and duration of the shunt. Based
on the patient history, clinical signs, plain radiography and electrocardiography it is possible to do a
clinical PDA classification based in 4 types as an anatomical and functional diagnosis without
resorting to angiocardiography or echocardiography.
Type 1 (small PDA):
- Asymptomatic left to right shunt.
- High frequency continuous murmur only at the left heart base.
- Pre cordial thrill is faint or not present at the left heart base.
- Heart rate and pulse quality are normal.
- Radiographs and ECG are normal even at 1-2 years of age.
- Surgery is not urgent but is recommended for normal life span.
Type 2 (medium size PDA):
- Asymptomatic left to right shunt.
- Coarse continuous murmur at the left heart base and slightly audible at the left apex.
- Palpable continuous thrill at left heart base
- Pulses normal or slightly bounding.
- Mild to moderate left heart enlargement before one year of age.
- Small to medium size ductus aneurysm may be present
- Borderline increase in pulmonary vascular markings.
- ECG Lead II R waves usually exceed 3 millivolts indicating left ventricular hypertrophy.
- Surgery is recommended but it can still wait a few weeks.
Type 3a (large PDA prior to congestive heart failure)
- Usually reduced exercise capacity.
- Coarse continuous murmur and thrill over most of the left thorax .
- Systolic murmur of mitral regurgitation often present at the left apex .
- Medium to large ductus aneurysm usually present .
- Marked left heart enlargement before 6 months of age.
- Significant increase in pulmonary vascular markings
- Pulses bounding due to wide pulse pressure
- ECG Lead II R waves may exceed 5 mV.
- Surgery recommended without delay.
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Type 3b (large PDA plus congestive heart failure)
- All 3a features plus dyspnoea due to pulmonary oedema.
- Usually poor body condition (cachexia).
- Atrial fibrillation occasionally seen in ECG.
- Pulmonary oedema must be cleared as much as possible with cage rest, oxygen, digitalization and
diuresis before surgery.
Type 4 (large PDA plus pulmonary hypertension)
- Right-to-left or balanced shunt
- Two weeks to 12 years old.
- Hind leg weakness or collapse with exercise.
- Cyanosis usually limited to caudal part of body.
- Pulses normal or weak.
- Polycythaemia (packed cell volume as high as 80%).
- Usually no murmur or precordial thrill after 1 month old.
- Split and/or prominent second heart sound often detectable.
- Right side apex beat stronger than left.
- Right axis deviation in electrocardiogram due to right ventricular hypertrophy.
- Large right heart and main pulmonary art e ry in radiographs.
- Peripheral pulmonary artery size can appear normal or decreased and show slight tortuosity.
- Surgery is contraindicated because of severe pulmonary vascular disease
- Treat polycythemia by periodic phlebotomy or chemotherapy.
Echocardiography
Transthoracic echocardiography (TTE) provides a non invasive examination that permits definitive
diagnosis of PDA by visualizing the shunt as well as evaluation of the hemodynamic consequences. In
a left-to-right shunting PDA, the left ventricular end-diastolic diameter is increased and generally
corresponds to the size of the PDA. Left ventricular end-systolic diameter tends to be normal in
young dogs and increased in older dogs. Fractional shortening is usually in the normal range but in
severe cases may be reduced. Evidence of systolic dysfunction (elevated left ventricular internal
diameter in systole, reduced fractional shortening) may be seen in dogs with large volumetric shunts
and typically persist or appears worse following successful ligation or occlusion. The left atrium is
usually enlarged to a similar degree as the left ventricle. Identifying continuous turbulent flow with
spectral and colour flow Doppler in the main pulmonary artery is characteristic of a PDA. The PDA
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itself can be visualized from the right parasternal short axis view and from the left parasternal
cranial view and it presents as a hypoechoic space between the pulmonary arterial trunk and the
aorta. Usually the left cranial short axis view provides the optimal image.
Spectral Doppler allows the evaluation of the Qp/Qs which gives the information of the shunt
fraction. Qp/Qs ≥ 2 means that the dimension of the ductus is from moderate to large. Peak velocity
through the ductus, when there is no increase resistance in the pulmonary artery, is between 4 and
6m/sec. Peak aortic velocity is frequently increased due to the volume overload and low pulmonary
resistance. Trans-aortic flow velocity may be as high as 3.75m/s with large shunts. This may lead to
an erroneous diagnosis of concurrent SAS. Therefore caution should be used when interpreting
aortic flows in patients with large shunts.
Although the ductus can be viewed by using transthoracic echocardiography, this technique is
postulated to be unsuited for achieving sufficient evaluation of PDA morphology in dogs. In order to
get complete information about PDA morphology is necessary to integrate the measurement of the
minimal PDA diameter and the ampulla diameter together with the ampulla length. TTE showed
limitations to properly measure PDA ampulla diameter. Furthermore PDA’s ampulla length is not
possible to be measured using transthoracic echocardiography because of the position of the PDA
and the descending aorta, being generally difficult or impossible to see the confluence of the 2
vessels. PDA ampulla diameter and length can be visualized and measured properly by angiography
as well as by transesophageal echocardiography (TEE). TEE uses a two-dimensional transducer at the
end of a flexible endoscope placed in the oesophagus capable of providing higher quality images in
result of a closer proximity to the heart, allowing a better visualization of the PDA. This contributes
to the understanding of the anatomical structure as has been demonstrated by angiography and
post-mortem examination.
We have observed that TEE provides accurate anatomic information regarding PDA morphology and
in some cases may be superior to angiography. We have to consider that optimal positioning of the
patient for angiographic viewing of the ductus does not always occur and overlying structures
interfere with the clarity. Also angiography is a radiologic method in which we are evaluating a
shadow of the heart and sometimes it may be very difficult to determine the real size and shape of
the ductus. Therefore, TEE may be an important echocardiographic tool to overcome these
angiographic limitations.
Right to left shunting PDA may be documented with echocardiography by injecting in the cephalic
vein micro bubbles contrast preparation (saline mixed with colloid solution) . In the right to left
shunt we see the micro bubbles in the abdominal aorta which normally should not be seen because
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of the pulmonary entrapment. If we see micro bubbles in the abdominal aorta means that the
bubbles had to bypassed the lungs through a reversed ductus.
Treatment
Uncorrected PDA often results in left-sided congestive heart failure with a mortality rate reported to
be greater than 60% within the first year. In some dogs, clinical signs are not apparent until they are
mature, but signs are present before the dog is 3 years old. In dogs older than 24 months almost
50% presented clinical signs such as cough, collapse, exercise intolerance, lethargy and dyspnoea.
So, the closure of PDA is always recommended.
Pharmacological
In human medicine the use of aspirin or indomethacin is described to induce closure of ductus in the
neonatal period. To be effective, this technique requires normal ductal muscle morphology. In dogs,
the patency is related to ductus muscle abnormality therefore this treatment is not effective. As
consequence, the approach “to wait until it closes” is equally ineffective. All patients with PDA
should undergo curative closure. Since the path physiology of the shunt leads to pulmonary
vasculature and cardiac damage a delay in the procedure is also contraindicated. Medical treatment
of a left-to right shunting PDA is aimed at treating heart failure. Medical management of a right-toleft shunting PDA is aimed at reducing the haematocrit.
Surgical
While surgical ligation has historically been the most utilized correction technique, interventional or
minimally invasive catheter-based procedures have become common over the past decade. Since
then, several devices has been used and published in veterinary medicine such as coils, Amplatzer
duct occluder (ADO), Amplatzer vascular plug and Amplatz canine duct occluder (ACDO). The
Amplatz canine duct occluder (ACDO) is a novel device for PDA occlusion in the dog and has rapidly
gained popularity since becoming commercially available. ACDO is a nitinol mesh device with a short
waist separating a flat distal disc from a cupped proximal disc. Specifically designed for this purpose,
this self-expandable device renders possible the treatment of PDA of varying sizes and
morphologies, in a wide range of dog weights and somatotypes. Its deployment is straightforward
and followed by rare complications if the size of the device is selected carefully according to the size
and shape of the ductus. Briefly, device size selection, and hence patient edibility, depends mainly
on the minimum ductal diameter (MD) and ductal morphology. Given the currently available ACDO
sizes, it should be possible to use this device to close PDA with a MD from 2 to 9 mm, considering
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that an over sizing factor (OF) of 1.5 to 2 between device waist diameter and MD is advised. Ductal
morphology is another very important aspect to consider when assessing the feasibility of this
technique. Successful ACDO deployment has been described for PDA of types IIA, IIB and III
according to Miller’s classification. Experience with type III PDA is however scarce and caution is
advised. Its tubular conformation and probable lack of support for the device may lead to instability
and embolisation. From the discussion above, one can easily understand that an accurate study of
PDA anatomical characteristics is of extreme importance when considering percutaneous treatment
with ACDO. Inaccurate device size selection may result in adverse events including systemic or
pulmonary embolisation, incomplete ductal closure, and haemolysis. Angiography has been
traditionally the recommended method for correct evaluation of PDA characteristics and ACDO size
selection, but TEE may contribute as well to this purpose. In a recent study we showed that TEE may
be used as a valid alternative to angiography in the evaluation of PDA dimensions in dogs, providing
correct ACDO size selection.
The use of TEE during the ACDO procedure facilitates the placement of the device trough the ductus
ostium and permit improved assessment of ACDO stability. The decrease in ductal flow associated
with clot formation can be viewed in real-time with a final assessment of the amount of reduced
ductal flow possible and quantifiable. TEE may be advantageous during these procedures by
providing superior anatomical information regarding PDA morphology, dimensions, ACDO
deployment, and ductal closure. Similar results have been observed by other authors during PDA coil
embolisation. So, TEE is an important tool for an easier ACDO deployment and confirmation of intraoperative ductal closure. Furthermore, use of TEE reduces the number of contrast injections
required and decrease fluoroscopy and anaesthesia time, leading to a reduction in radiation
exposure and cost.
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PULMONIC STENOSIS (PS)
Introduction
Pulmonic stenosis is one of the most common congenital heart defects in dogs. Pulmonic stenosis
can be classified in 3 types, according to the localization of the lesion along the right ventricular
outflow tract (RVOT), as subvalvular, valvular and supravalvular. The most common type is valvular
pulmonic stenosis which also can be subdivided in two different types: type A and type B; both types
of stenosis may coexist in some patients determining a mixed type pulmonic stenosis. Type A
pulmonic stenosis is the most frequent type observed in veterinary clinics.
Anatomical and functional considerations
Pulmonic stenosis, in contrast to subaortic stenosis, usually presents with its definite grade of
severity early in the life of the affected puppy. We have to consider, though, that pressure gradients
may increase during the growing period so mild pulmonic stenosis in a 4 months old dog usually
progresses to a moderate or severe stenosis at 1st year of age based on pressure gradients.
In humans, valvular stenosis is subdivided into dysplastic valve leaflets with annular hypoplasia and
no post stenotic dilatation, and cases with non-dysplastic valves and fused leaflets. In veterinary
medicine, have been published similar criteria of subdivision differentiating PS into 2 main types:
Type
A
• The annular size is normal . Various degrees of leaflet
thickening with incomplete separation of the commissures to
almost complete fusion. It causes a systolic doming of the
valve (“windsock” type image) with most often eccentric
valvular opening with various degrees of reduced crosssectional area. Poststenotic dilatation of the pulmonary trunk
is present with various degrees of severity.
Type
B
• The pulmonary ostium is hypoplastic , with various degrees of
valvular leaflet thickening and immobility, but little
commissural fusion . The main pulmonary trunk is also often
hypoplastic , and rarely has a poststenotic dilatation.
Type A pulmonic stenosis is the most common type of valvular PS observed.
Primary subvalvular obstructions by an infundibular fibrous ring, analogous to SAS, appear to be rare
in dogs. Secondary stenosis of the infundibulum with various degrees of fibromuscular infundibular
hypertrophy, as a result of pressure-induced hypertrophy, due to pulmonic stenosis is well described
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and is the more common form of subvalvular PS; likely, it has a dynamic component and leads to
worsening of the stenosis with exercise or stress.
Primary infundibular stenosis has been sporadically reported in humans, dogs, and cats. This rare
form of stenosis divides the right ventricle into a proximal ‘‘high pressure’’ chamber and a distal
‘‘low pressure’’ chamber and has been attributed to (1) anomalous muscle bundles; referred to as
double chambered right ventricle (DCRV) and (2) a fibrous diaphragm or fibromuscular band of
tissue obstructing the infundibulum; referred to as infundibular pulmonic stenosis in humans.
In some breeds, especially the English bulldog and Boxers, an anomalous R2A-type left coronary
artery encircles and constricts the right ventricular outflow tract. This anomaly represents an
exclusion criteria for any valvuloplasty procedure, as a dilation of the infundibulum would lead to
severe coronary ischemia and the patient’s demise.
Isolated supravalvular PS appears to be extremely rare. Attention should be taken during the
ecocardiographic examination of the systolic doming of the valve in type A PS cases because
supravalvular PS could be easily misdiagnosed.
Combination of SAS and PS occurs in a considerable number of boxers. In one retrospective study of
500 Boxers a combination of the SAS and PS occurred in 24% of dogs with cardiac disease.
In a recent study it has been observed associated congenital cardiac defects in 32% of dogs with
pulmonic stenosis. The most common associated congenital anomalies were subaortic stenosis
followed by ventricular septal defect and patent ductus arteriosus.
Genetics and Breeds
A heritable basis for pulmonic stenosis has been shown in Beagles and Keeshonds based on breeding
studies. Other breeds at increased risk for pulmonic stenosis include:

English Bulldog

Fox Terrier

Miniature Schnauzer

Chihuahua

Beagle

Samoyed

Boxer

Bull Mastiff

American Cocker Spaniel

West Highland White Terrier
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Boykin Spaniel
In Oliveira’s study (2011), the most commonly affected breed is the Boxer with 38% of PS cases
followed by English Bulldog (9%), Mixed breed (7%), French Bulldog (6%) and Beagle (4%). The other
multiple breeds were ≤ 3% of dogs.
Although it is considered that both sexes are affected equally a male predominance has been
reported for the English Bulldogs and Bull Mastiff.
Pathophysiology
Irrespective of the obstruction’s location the main hemodynamic consequence of pulmonic stenosis
is an increased right ventricular systolic pressure and wall stress leading to right ventricular
hypertrophy. Leftward septal deviation or flattening, and an increased systolic pressure gradient
across the pulmonary valve are observed. The magnitude of the resultant pressure gradient is
directly related to both the quantity and rate of blood flow across the obstruction and to the crosssectional area of the stenotic region. The pressure gradient is commonly used as an index of the
lesion severity. Distal to the obstruction, blood flow velocity increases and becomes turbulent
determining in some cases a main pulmonary artery enlargement also called pos-stenotic dilation.
The right ventricular hypertrophy try to normalize the increased wall stress, following Laplace’s law,
as well as try to normalize right ventricular systolic function trying to maintain the right ventricular
stroke volume within the normal range. This right ventricular hypertrophy will also determine a
reduced ability of the ventricle to fill properly determining also a diastolic dysfunction.
With the progression of the disease, a right side congestive heart failure develops due to an
increased right atria dimensions and right ventricular systolic dysfunction.
Progressive right atria enlargement results from various factors including elevated right ventricular
diastolic pressure, secondary tricuspid regurgitation caused by high systolic pressure and geometric
changes within the right ventricle, right ventricular hypokinesia (right ventricle loses the force of
contraction in a similar way as does left ventricle in advanced cases of aortic stenosis) and decreased
cardiac output with compensatory retention of sodium and water.
When elevated peak velocities are found in the RVOT, the values are then transformed into an
estimated pressure gradient with the simplified Bernoulli equation (ΔP=4v2):
Mild stenosis
Moderate stenosis
Severe stenosis
• Gradient under 50 mmHg
• Gradient between 50-80 mmHg
• Gradient over 80 mmHg
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Natural history depends on lesion severity. Dogs affected by mild and even moderate PS may live
normally. Animals with moderate-to-severe stenosis may develop complications, including
exertional syncope, cardiac arrhythmias, secondary tricuspid regurgitation, atrial fibrillation, right
congestive heart failure and sudden death. Systolic pressure gradients are not always predictive of
clinical outcome but a general correlation can be observed between pressure gradient and survival.
Diagnosis
Clinical presentation:
Usually dogs are asymptomatic showing only a left basilar ejection murmur over the pulmonic valve
that radiates to the left craniodorsal cardiac base and in some cases it can also radiate to the right
craniodorsal base. In general the intensity of the murmur increases with the severity of obstruction.
The murmur is a classic ejection-harsh sound with crescendo-decrescendo quality. Rarely a diastolic
murmur of pulmonic insufficiency can also be heard. It is not uncommon to auscultate a holosystolic
murmur of tricuspid regurgitation over the right hemi thorax.
Some cases present with ascites, exercise intolerance and syncope related to right-sided congestive
heart failure and low cardiac output. Arrhythmias and reflex-mediated syncope are other causes for
collapse. Sudden death without premonitory signs is rare but may occur. Clinical signs are more
likely to occur in dogs older than 1 year of age. Symptoms may develop earlier in dogs with severe
stenosis or with the presence of other congenital cardiac abnormalities such as SAS, ventricular
septal defects and PDA.
Radiography
Thoracic radiographs provide little information regarding the severity of the stenosis since they are
usually normal in mild to moderate affected animals although right-sided cardiomegaly may be
present. In moderate to severely affected patients a prominent right heart enlargement may be
observed and dogs with Type A pulmonic stenosis a post-stenotic dilation of the main pulmonary
artery can be seen. Pulmonary underperfusion may also be observed depending on the severity of
the stenosis.
Electrocardiography
Electrocardiography may be completely normal or may show a pattern of right-sided enlargement
especially in severe cases with marked right ventricular hypertrophy; ventricular arrhythmias and
supraventricular arrhythmias may also be present. In some cases Holter monitoring may be useful.
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Echocardiography
Echocardiographic examination is the most important diagnostic tool in order to identify the
presence of this congenital heart defect as well as permits to classify the different types and severity
of PS. The right ventricular outflow tract has to be optimized in its entire length with a perfect long
axis view although it may be difficult in many cases due to its curved course. Initially an oblique,
somewhat tangential section of the RVOT, obtained from a right parasternal short axis view, can be
generated in all dogs which permit to measure appropriately the pulmonary annulus. Then, this
projection may be optimized by moving the probe towards the sternum, maintaining the same angle
section, trying to visualize the maximum length of the RVOT, pulmonary annulus and main
pulmonary artery; this last view permits the best alignment to perform spectral and colour flow
Doppler recordings. In patients with subvalvular PS, these views are sufficient to image subvalvular
narrowing caused by muscular infundibular hypertrophy, fibrous diaphragm or fibromuscular band,
as well as to observe the presence of a dynamic stenosis, which is not uncommon. Dynamic stenosis
is well observed with the spectral Doppler characterized by a “knife” shaped flow pattern. A
differential diagnosis of DCRV and an anomalous R2A-type left coronary artery has to be done in all
patients with subvalvular PS.
Usually cases with valvular PS can be studied properly using this right side view, observing also a
thickened and hypertrophic right septum and RV free-wall with some hyperechoic areas relative to
endomyocardial fibrosis, especially in severe cases. Left side views are mandatory in order to
complete the echocardiograhic examination. Left cranial parasternal short axis view is obtained
doing a steep dorsal and slightly more cranial angulation after obtaining a long axis view of the aortic
root; this view shows the RVOT with the main pulmonary artery in most of its length and also the
pulmonary bifurcation. This view displays valvular abnormalities. Another suggestive finding of
pulmonic stenosis that may be observed is the presence of post-stenotic dilatations, although this
feature is not present in type B phenotype. Echocardiography also allows determination of the
severity of right ventricle hypertrophy or altered kinetics as in the presence of paradoxical motion or
flattening of the septum. These findings are also strongly suggestive of increased RV pressure.
However, a non-invasive estimation of increased pressure can only be obtained by measuring
pulmonary peak velocity with the continuous wave Doppler beam in parallel alignment with the
direction of flow. This usually is accomplished from either the right or left cranial parasternal
windows. The values obtained are then transformed into an estimated pressure gradient with the
simplified Bernoulli equation. Tricuspid annulus dilatation is also an important aspect to evaluate as
well as the high velocity tricuspid regurgitation. Colour Doppler may also identify associated
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congenital defects such as ventricular muscular defects, or dynamic obstruction in the left
ventricular outlet related to altered ventricular geometry.
In some cases transesophageal echocardiography (TEE) may be a complementary tool to study the
subvalvular, valvular or supravalvular anatomy especially in those cases with deficient
echocardiographic window or structural thoracic abnormalities.
Treatment:
Special consideration
Patients with resting gradients of over 80 mmHg are at risk of sudden death and balloon
valvuloplasty is recommended whether the patient is symptomatic or not. Patients presenting
intermediate resting gradients (50-80 mmHg) often live normal lives although long term prognosis is
uncertain. In these patients, therapeutic decision is determined by the clinical presentation
(presence of clinical signs), degree of RV hypertrophy and the nature of the progression. Patients
presenting low resting gradients (under 40-50 mmHg) usually live normal lives and therapy is
unnecessary.
Pharmacological
The decision to treat pulmonic stenosis is based on the severity of clinical signs, the magnitude of
the pressure gradient across the pulmonic valve and degree of RV hypertrophy. The pressure
gradient for which a medical treatment should be recommended cannot be stated with certainty.
Usually with a pressure gradient greater than 50-60mmHg a medical treatment based on betablocking agent could be started. This drug reduce myocardial oxygen demand and increase coronary
perfusion by decreasing heart rate and contractility; these effects may help in preventing or at least
reducing the incidence of the late stage characterized by a right ventricular myocardial insufficiency.
Also this drug reduces the dynamic stenosis at the RVOT as it reduces the heart rate and contractility
as well as reduces ventricular arrhythmias, syncopal events and may prevent sudden death. The
reduction of the dynamic stenosis and arrhythmias is very important in those cases where a
pulmonary balloon valvuloplasty will be performed. Atenolol is used with a starting dose of
0,2mg/Kg SID or BID and progressively increased (weekly increments) up to 0,5-1 mg/Kg SID or BID
always with blood pressure and ECG monitoring.
Surgical
Pulmonary balloon valvuloplasty (BVP) is the first line of treatment for PS. Valvuloplasty should be
performed in any symptomatic patient and in any patient with severe pressure gradient with RV
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hypertrophy (even if they are asymptomatic) as soon as PS is diagnosed. Delay in the treatment can
lead to progression of RV and infundibular hypertrophy, not only making the procedure technically
more difficult but also diminishing the immediate response to therapy.
In one retrospective study in which BVP was performed in 95 dogs we documented a significant
reduction of pressure gradient after the procedure at 24h and at 1 year either for type A and type B
pulmonic stenosis. The mean pressure gradient after the procedure at 24h and at 1 year between
group A and B resulted to be lower in type A, suggesting better results. The PBV was considered
successful (more than 50% reduction in pressure gradient from baseline) in 65 dogs with type A
(90%) and in 7 dogs with type B (54%). The PBV was performed without significant complications in
93% of dogs. Based on these data we could say that PBV is effective in type A and B PS, being even
more effective in type A. In human literature similar results are reported. The PBV of patient with
dysplastic valve was less effective (61, 11%) when compared with those with typical PS (80, 59%).
Despite the success rate was lower in the dysplastic group, PBV is still considered the first treatment
option in both types of PS in humans. Furthermore PBV in type B (or dysplastic) may avoid or delay
the need of surgery and provides a good long outcome in dogs as it occurs in humans.
In a study involving 120 pulmonary BVPs in dogs (Oriol Domenech, personal data), the major
complications observed were: right ventricle perforation, ventricular tachycardia, ventricular
fibrillation and severe bradycardia with asystole. The major complication rate during PBV were
around 4.8% and death rate about 2.4%. Right ventricle perforation with a consequent pericardial
effusion and presence of the contrast in pericardial space, is the most spectacular complication we
have seen but it did not determine pericardial tamponade nor death. S-T segment depression, as a
sign of myocardial ischemia, is of great importance because is related to an increased risk of severe
ventricular tachycardia. Mortality during BVP was mainly due to life threatening ventricular
arrhythmias. Ventricular tachycardia usually responded very well to lidocaine infusion unless there
is a severe myocardial ischemia. These complications are related to material, procedure technique,
size of patient, patient stability before the procedure, RV hypertrophy degree with presence of
fibrosis, type of the stenosis and experience of the operator. We also have observed that patients
pre-treated with beta-blocking agents presented much less incidence of malignant arrhythmias as
well as less worsening of the dynamic pulmonic stenosis. In some patients with significant
infundibular hypertrophy is possible to observe a worsening of the dynamic pulmonic stenosis after
the valve dilation due to the decreased resistance of the RVOT that determines an exaggerated
systolic motion of the infundibular area of the RVOT. This is a very important feature because it may
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evoke to a suicide infundibulum and patient death. This is one of the reasons why we pre-treat with
a beta-blocking agent (atenolol) all patients that will be performed a BVP.
We can also find errors of the catheterisation that can complicate or not all the procedure, being the
most frequent: contrast tattoo, air bubble, inappropriate localization of the catheter during contrast
injection and guide wire loop formation in the right atrium or right ventricle.
It is already well known that anomalous left main coronary artery (originating from a single right
coronary artery) which encircles the stenotic RVOT, is present in some affected dogs, especially in
English Bulldogs and Boxers, so coronary anatomy examination with echocardiography or a selective
coronario-angiography is imperative. Balloon dilation in these patients has been reported to cause
rupture of the artery and sudden death of the patient.
Recheck evaluations are typically performed 3, 6 and 12 months after the procedure and then
annually. Gradients may continue to decrease in the first 3 to 6 months, if we compared with 24h
post-procedure gradient, probably due to resolution of the valve oedema following balloon dilation
and regression of RV/infundibular hypertrophy. So determination whether BVP has been successful
should not be judged until several months following the procedure. We usually continue with beta
blockers in dogs with residual pressure gradient ≥ 60-80mmHg, RV hypertrophy and residual
dynamic RV outflow obstruction.
AORTIC STENOSIS (AS)
Introduction
Aortic stenosis can be classified in 3 types, according to the localization of the lesion along the left
ventricular outflow tract (LVOT), as subvalvular, valvular and supravalvular. The most common form
is subvalvular, commonly referred to as subaortic stenosis (SAS), and can be subdivided into three
different types: type 1, type 2 and type 3.
Canine subaortic stenosis is the second most frequent congenital heart defect in some studies. The
incidence has been estimated to be between 22 and 34 percent of the reported canine congenital
heart disease although geographic variation in prevalence is an important factor.
Anatomical and functional considerations
The subvalvular lesion may be present at birth or may develop during the first weeks / months of
life. In pathology studies of SAS in the Newfoundland, subvalvular lesions were detected only in pups
that were older than 3 weeks. Based on this finding, SAS is not strictly congenital but rather develops
early in life. This observation has also been reported in humans. It has been speculated that the
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lesion arises due to morphological abnormalities in the LVOT that increase shear stress and induce
proliferation of cells in the LVOT. This proliferation may be derived from persistent embryonic
endocardial tissue that retains its proliferative capacity. In dogs, the obstruction may progress for
the first 12 months of life. This progression is important in order to correctly identify pups of breeds
known to be at risk for this disease and it is probably inappropriate to “clear” dogs for subaortic
stenosis before they are full grown. A full certification of phenotipically normal dogs can only be
issued after 12 months of age .Additionally, pressure gradients may also increase in affected dogs
during the growing period so that a mild aortic stenosis at the age of 4 months usually progresses to
a severe aortic stenosis at in the first year. So, whenever mild-to-moderate SAS has been
documented in a young dog, no prognosis should be given, because the obstruction may, and often
becomes, more severe.
Three different types of subaortic stenosis have been described based on necropsy findings and with
increasing severity of the disease from type 1 to 3:
The ventricular surfaces of the aortic valve leaflet may also be thickened and this may induce
sometimes a misdiagnosis of valvular aortic stenosis, therefore it is very important to carefully
evaluate the LVOT.
The most frequent forms observed, are type 1 and 2 representing 85% of all SAS cases.
Apart from the fixed subaortic lesion, a dynamic (labile) component may also affect the behaviour of
the SAS. In the fixed stenotic lesion the severity of the stenosis does not change from beat to beat or
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during the systolic phase. In contrast, the dynamic component of the stenosis may change with heart
rate, contractile state or during the systolic phase. The hypertrophied muscle at the left ventricle
outflow tract or the septal anterior motion of the mitral valve are classic examples of dynamic
stenosis that may accompany SAS.
Genetics and Breeds
Subaortic and valvular aortic stenosis are propagated in breed and families with a genetic basis but
the clear mode of transmission is not completely understood yet. The genetic basis is suspected of
being polygenic or domininant autonomic with gene modifiers. Because inheritance of SAS is not
explained by simple Mendelian genetics, dogs with mild SAS may have severely affected offspring. As
a result, detection of mild SAS is important despite the fact that mild outflow tract obstruction
usually does not have clinical consequences. Although breed predisposition (most often large- and
giant breeds) has been identified there is no sex predisposition:
•
Newfoundland
•
German Shepherd
•
Boxer
•
Golden Retriever
•
Rottweiler
Pathophysiology
Irrespective of the obstruction’s location, the main hemodynamic consequence of aortic stenosis is
an increased resistance to the left ventricular systolic flow. The increase in afterload verified in
subaortic stenosis leads to an increase in the left ventricular systolic pressure (an increase in the
pressure gradient across the stenotic lesion), an increase in blood flow velocity through the lesion
and left ventricular concentric hypertrophy. The left ventricular hypertrophy is usually proportional
to the severity of the obstruction and tries to normalize: systolic wall stress, ventricular systolic
function and left ventricular stroke volume. A severe concentric hypertrophy may reduce the enddiastolic volume and produces an increase in ventricular stiffness which may reduce the ability of the
ventricle to fill properly determining a diastolic dysfunction. Also, chronic and severe left ventricular
pressure load can result in the development of systolic myocardial dysfunction. Late in the course of
the disease we can observe an “after load mismatch” which is characterised by dilation and
hypocontractility of the left ventricle determining also a moderate-to-severe mitral regurgitation; in
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this scenario the peak aortic velocity and gradient is reduced due to the myocardial failure and signs
of left congestive heart failure may occur.
SAS is associated with arteriosclerotic lesion of the intramural coronary arteries. Abnormally narrow
coronary vessels, large myocardial mass, and increased left ventricular systolic pressure contribute
to the development of myocardial ischemia leading to a predisposition for ventricular arrhythmias.
Diagnosis:
Clinical presentation
Boxers will commonly exhibit a 1/6 to 2/6 systolic ejection murmur without any heart disease. It is
reported that boxers have a smaller left ventricular outflow tract and aortic trunk than other breeds
relative to the left ventricular diameter and volume. This could lead to an increased blood flow
velocity and turbulence. This turbulence is heard as a mild intensity heart murmur. Pathological
cases present a systolic ejection murmur loudest in the left basilar region that radiates often toward
the right cranial thorax. In mildly or moderately affected dogs, a grade 1-4/6 systolic murmur can be
heard best in the left 4th -5th intercostal spaces at the costochondral junction. Severely affected dogs
usually have a grade 4-6/6 systolic murmur often with precordial thrill.
At the time of the initial diagnosis patients with mild or moderate SAS are usually asymptomatic and
owners report a normal and apparently healthy individual when presenting the dog for routine
examination showing a heart murmur as the only physical examination finding. Some severely
affected animals may be presented for exertional fatigue, syncope or signs referable to congestive
left heart failure. Another clinical finding revealed in severe SAS patients is a weak femoral pulse
(parvus and tardum) due to the compromised and delayed left ventricular ejection volume.
Arrhythmias may also be present on the time of examination. Sudden death without premonitory
signs may occur.
Radiography
Thoracic radiographs are usually normal in mild to moderate affected animals since the pattern of
concentric hypertrophy does not increase the cardiac silhouette dimensions. The most common
finding in severely affected dogs is enlargement of the aortic root (post-stenotic dilatation). In
patients with afterload mismatch signs of left sided congestive heart failure may be observed.
Electrocardiography
Morphological abnormalities of the electrocardiogram are usually not observed. Evidence of left
ventricular hypertrophy may be detected in severely affected patients. Ventricular premature
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contractions or ventricular tachycardia may occur in severe cases that may be induced or
exaggerated by exercise. Holter monitor recordings may be of interest in patients with moderate-tosevere SAS to detect ventricular arrhythmias and ST segment changes that might suggest an
increased probability of sudden death.
Echocardiography
Echocardiographic examination is the most important diagnostic tool in order to identify the
presence of this congenital heart defect as well as to classify the different types and severity of SAS.
For detection of subaortic stenosis, a careful evaluation of the left ventricular outflow tract
morphology must be performed with 2D echocardiography. The dimension and morphology of the
aortic annulus and valve cusps are evaluated from the standard right parasternal long axis view
optimizing the LVOT and right parasternal short axis view. In some cases post-stenotic dilation of the
ascending aorta is observed and can be identified very well from left parasternal cranial long axisview optimizing LVOT. The aortic valve often appears mildly thickened due to the continuous trauma
associated with the stenotic jet as well as appears hypo mobile due to the reduced flow through the
aorta. Trans-valvular aortic flow must be measured using spectral Doppler, with the transducer
placed caudal to the xyphoid process of the sternum to obtain a subcostal view. Pulsed-wave
Doppler and colour flow Doppler studies in the LVOT and aorta demonstrates a broad systolic
turbulent jet. Continuous-wave Doppler examination is important in order to know the peak aortic
velocity and gradient. The use of 3.5 MHz or lower frequency transducers is advised in order to
assure sufficient penetration of the tissues and adequate signal strength of the Doppler recordings,
as the distance to the aortic valves is quite far in large dogs with the subcostal view. Standard left
apical 5 chamber view is also a good alternative but should only be used if subcostal images and
measurements are not feasible under any conditions.
In order to correctly identify dogs affected with aortic stenosis, the following criteria are suggested:
- Heart murmur on cardiac auscultation
- Direct ultrasonographic imaging of the anatomic obstructive lesions:
o
Type 1: small nodules
o
Type 2: fibrous ring
o
Type 3:concentrically narrowing tunnel
- Identification of a turbulent aortic flow as assessed by pulse-wave Doppler using high pulse
repetition frequency at the highest velocity, with peak velocity on continuous-wave Doppler of >
2m/s averaged over 3 cardiac cycles in periods of stable sinus rhythm.
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Spectral Doppler gives you the possibility to determine the presence of a fixed or dynamic stenotic
component.
Continuous-wave Doppler permit to determine the highest peak velocity, the values are then
transformed into an estimated pressure gradient with the simplified Bernoulli equation (ΔP=4v 2).
The obtained values are used to classify the severity of the stenosis:
Mild stenosis
Moderate stenosis
Severe stenosis
• Gradient under 50 mmHg
• Gradient between 50-80 mmHg
• Gradient over 80 mmHg
It is important to recognize that the pressure gradient across the lesion is flow-dependent, meaning
that the pressure gradient depends not only on the cross-sectional area of the stenotic orifice but
also on stroke volume. Sympathetic activation associated with restraint and disorders such as aortic
valve regurgitation, patent ductus arteriosus or marked bradycardia increase forward stroke volume
and therefore peak aortic velocity. On the other hand factors that decrease stroke volume such as
myocardial dysfunction, sedatives, anaesthetics and mitral regurgitation may decrease aortic
velocity. Therefore, the flow dependence of peak aortic velocity limits the usefulness of pressure
gradient as a single index of stenosis severity.
Treatment
Pharmacological
Medical treatment is based mainly on the use of beta-adrenergic blocking agents although there is
lack of data comparing treated versus untreated dogs. The presumed effect of beta-blockers relates
to the decrease in myocardial oxygen demand and increase in coronary perfusion by decreasing
heart rate and contractility. These effects may prevent further myocardial ischemia associated with
left ventricular hypertrophy, increased systolic wall stress and abnormal coronary flow dynamics
reducing also the incidence of lethal ventricular arrhythmias. It is possible that the effects of betablockade reduce the arrhythmogenic effects of catecholamine on diseased myocardium, decreasing
the frequency and potentially fatal arrhythmias. However evidence to support this contention is
lacking. We usually use atenolol starting at 0,2mg/Kg SID or BID and titrate to effect performing
always an electrocardiogram and blood pressure measurement before any increment of the dose.
Occasionally medical management of congestive heart failure is necessary. In these cases diuretic
therapy and ACE-inhibitors are indicated.
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Interventional Cardiology (Balloon dilation)
In a recent report short-term reduction of the peak systolic pressure gradient was found but no longterm benefit in survival times was observed when compared to a group of dogs receiving atenolol.
The disappointing results obtained with balloon dilation depend on the location and the nature of
the stenotic lesion. Based on this data percutaneous balloon valvuloplasty is not indicated for SAS.
Further Reading:
1. Bonagura JD, Lehmkuhl LB. Congenital heart disease. In Fox P : Textbook of canine and feline
cardiology 1999: 471-535
2. Bussadori C, Amberger C, Le Bobinnec G, Lombard CW. Guidelines for the echocardiographic
studies of suspected subaortic and pulmonic stenosis. J Vet Cardiol 2000; 2:17-24.
3. Bussadori, C., M. Carminati, Domenech O. Transcatheter closure of a perimembranous ventricular
septal defect in a dog. J Vet Intern Med 2007; 21(6): 1396-400.
4. Gordon SG, Miller MW, Roland RM, Saunders AB, Achen SE, Drourr LT, Nelson DA, Transcatheter
atrial septal defect closure with the Amplatzer atrial septal occluder in 13 dogs: short- and midterm outcome in J Vet Intern Med. 2009 Sep-Oct;23(5):995-1002.
5. Johnson, M. S., M. Martin, et al. Pulmonic stenosis in dogs: balloon dilation improves clinical
outcome. J Vet Intern Med 2004; 18(5): 656-62.
6. Oliveira et al. Retrospective Review of Congenital Heart Disease in 976 Dogs. Journal of
Veterinary Internal Medicine. 2011; 25: 477–483
7. Oyama MA, Sisson D, Thomas W P et al. Congenital heart disease. In Ettinger SJ: Textbook of
veterinary internal medicine 6th 2005 : 972-1021
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